/ » SAJOUS'S Analytic Cyclopedia OF Practical Medicine CHARLES E. de M. SAJOUS, M.D., LL.D., Sc.D. ASSISTED BY LOUIS r. de M. SAJOUS, B.S., M.D. WITH THE ACTIVE CO-OPERATION OF OVER ONE HUNDRED ASSOCIATE EDITORS NINTH REVISED EDITION 1[llustrate^ witb jf ulUpaoe 1balt*tone ant> Color plates an& Hppropriate Cuts in tbe Xleit Volume One oi of • 5 ■ oJ ai PHILADELPHIA F. A. DAVIS COMPANY. PUBLISHERS 1922 COPYRIGHT, 1922 BV F. A. DAVIS COMPANY Copyright, Great Britain. All Rights Reserved VI PRINTED IN U. S. A. PRESS OF F. A. DAVIS COMPANY PHILADELPHIA. PA. PREFACE TO THE NINTH EDITION The preceding edition, as stated in its preface, incorporated the new lines of thought opened up. modified or indirectly influenced by the war. This applied not only to surgery as generally believed, but also practically to every disease to which the human male is heir, including various tropical disorders brought to the seat of active opera- tions by troops and laborers from Asia. Africa, etc.. where such dis- eases prevailed. The aftermath of this great aggregate of clinical observations engendered a period of intensive study calculated to estab- lish on a solid footing the deductions hastily vouchsafed. The present, or ninth edition, even though issued but two years after its predecessor, has for its purpose to present what suggestive data of this character have been recorded during this brief period. \\'hile the majority of subjects reviewed in the work have been more or less added to or altered, some have required considerable readjustment, those of Frac- tures and Dislocations for instance, which have been brought up to date by Professor W. Wayne Babcock who. as Lieutenant-Colonel and Chief Surgeon of one of the greatest of our military hospitals during the war, treated an enormous number of injuries of all sorts. It was also suggested in the previous edition that as much of the materia! incorporated therein might ultimately have to be modified through elucidative inquiry carried on after the excitement accom- panying or immediately following strife had been allayed, the newer data presented at the time had l:)een introduced in small type, the larger type text being intended only to portray those features of our knowledge which prolonged experience in practice had sanctioned. In the short space of two years, the data thus poised on a permanent foundation may be said to have been few. but wherever this seemed warranted, they were introduced in the large type text. In some (iii) iv PREFACE. directions other than those connected with the war, as in the manage- ment of the disorders of parturition, the endocrinopathies, protein sensitization, protein therapy, adenoid vegetations, etc., greater latitude was afforded and taken advantage of. The transitions in all branches of medicine are so numerous that the value of the present edition will be perpetuated by periodical sup- plements which, following up each clue in the eight volumes, will enable their readers to keep well abreast of the times without being obliged to purchase a new Cyclopedia. C. E. DE M. Sajous. CONTRIBUTORS TO VOLUME I. ROBERT T. MORRIS. M.D.. Professor of Surgery, Post-Graduate Medical School, New York City. ERNEST LAPLACE. M.D., LL.D., Professor of Surgery, University of Pennsylvania Graduate Medical School, Philadelphia, Pa. A. H. WRIGHT. B.A.. M,D.. Late Professor of Obstetrics, University of Toronto, Toronto, Ont. JOHN B. DEAVER, M.D., Professor of Clinical Surgery. University of Pennsylvania Medical School, Phil.-^delphia, Pa. FRAXXIS X. DERCUM. M.D., Professor of Nervous and Mental Diseases, Jefiferson Medical College, Philadelphia, Pa. JAY F. SCHAMBERG. A.B., M.D.. Professor of Dermatolog}', Jefferson Medical College, Philadelphia, Pa. P. E. LAUNOIS, M.D., Sc.D.. Professor Agrege of Medicine in the Faculty of Paris, AND M. H. CESBROX, M.D., Paris, France. RUFUS B. SCARLETT. M.D.. Formerly Assistant Physician in the Department of Laryngolog3% University of Pennsylvania Medical School, Trenton, N. J. J. P. LAXGLOIS. M D.. Professor Agrege of Medicine in the Faculty of Paris, Paris, France. W. WAYXE BABCOCK. AM.. M.D.. Professor of Surgery and Clinical Surgery, Temple University Medical School, Philadelphia, Pa. (v) VI CONTRIBUTORS TO VOLUME I. FREDERICK P. HENRY, A.M., M.D., Professor of Medicine, Woman's Medical College, Philadelphia, Pa. AND NORMAN P. HENRY, M.D., Physician to Pennsylvania Hospital, Philadelphia, Pa. HOWARD S. HANSELL. M.D., Professor of Ophthalmology, Jefferson Medical College, Philadelphia, Pa. HERMAN F. VICKERY, M.D., Assistant Professor of Medicine, Harvard University Medical School, Boston, Mass. HENRY D. JUMP, M.D., Visiting Physician to Philadelphia General and Misericordia Hospitals, Philadelphia, Pa. WALTER L. CARTSS. M.D.. Assistant Instructor in Laryngology, University of Pennsylvania Medical School, and Visiting Physician to Presbyterian Hospital, Philadelphia, Pa. F. LEVISON, M.D., and A. ERLANDSEN, M.D., Copenhagen, Denmark. C. SUMNER WITHERSTINE, M.S., M.D.. Lecturer on Pharmacology, Temple University Medical School, Philadelphia, Pa. E. E. MONTGOMERY, M.D., LL.D., Professor of Gynecology, Jefferson Medical College, Philadelphia, Pa. C. E. deM. SAJOUS, M.D., LL.D., Sc.D., Professor of Applied Endocrinology in the University of Pennsylvania Graduate Medical School and of Therapeutics in the Temple L^niversity Medical School, Philadelphia. Pa. L. T. DE M. SAJOUS. B.S., M.D., Associate Professor of Pharmacology, Temple University Medical School and Instructor in Endocrinology in the University of Pennsylvania Graduate Medical School, Philadelphia, Pa. CONTENTS OF FIRST VOLUME. PAGE Abdomen, Surgery of 1 The Fourth Era in Surgery . , , 1 Anteoperative Management 3 Instruments and Apparatus 6 Local Anesthesia 9 Postoperative Treatment 10 Postoperative Complications 12 Shock \ 12 Meteorism 13 Acute Dilatation of the Stomach . . 14 Meteorism Due to Mechanical Ob- struction of Bowel 14 Colon Bacillus Nephritis 15 Meteorism Due to Extension of Peritonitis 16 Poisoning by Bichloride of Mercury and by Iodoform 17 Uncontrollable VomJting 18 Properitoneal Hernia 18 y Hernia into a Rent in the Omentum. 18 Perforation of the Bowel 18 Postoperative Phlebitis 18 Pylephlebitis 19 Secondary Abscess 19 Mesenteric Thrombosis 19 Bladder Complications 19 Postoperative Psychoses 19 Peritoneal Adhesions 20 Postoperative Pneumonia 20 Pleurisy 21 Fistulae 21 Objects Left Behind 22 Secondary Hemorrhage 23 Toilet of the Peritoneum 24 Drainage of the Peritoneal Cavity ... 25 Hemostasis 28 External Incisions 29 Exploratory Operations 35 Peritoneal Adhesions 35 Intestinal Sutures 3S Surgical Diseases of the Stomach .... 41 Gastric and Duodenal Ulcers 41 Carcinoma 43 Concrenital Stenosis of Pylorus .... 44 Hour-glass Stomach 46 Non-obstructive or Atonic Dilata- tion 46 Gastroptosis 47 Foreign Bodies 47 Stricture of the Esophagus 47 Typical Operations Upon the Stom- ach 47 Gastroplication 47 Gastric Omentoplication 48 Gastrotomy 49 Pvloroplasty (Heinecke-Mikulicz Operation) 49 Pyloroplasty by Finney's (Gould's) Method and Gastroduode- nostomy 50 PAGE Abdomen, Surgery of, Typical Opera- tions Upon the Stomach {continued). Gastrostomy 51 Gastrorrhaphy 53 Gastroplasty 53 Gastrogastrostomy 53 Partial Gastrectomy 53 Complete Gastrectomy 56 Surgical Diseases of the Peritoneum. 56 Septic Peritonitis 56 Tuberculous Peritonitis 59 Ascites 60 Omentopexy or Talma-Drummond Operation 61 Surgery of the Mesentery and Omentum 61 Surgical Diseases of the Intestines.. 62 Ileus 62 Volvulus 63 Intussusception 64 Typhlitis 65 Meckel's Diverticulum 65 Colonic Diverticula 65 Wounds, Perforation from Within, etc 66 Typical Operations of the Intestine .. 66 Enterorrhaphy 66 Enterectomy . 67 Enteroanastomoses 68 Gastroenterostomy 69 .Anterior Gastroenterostomy 71 Posterior Gastroenterostomy 71 End-to-end Anastomosis after En- terectomy 74 Lateral Anastomosis 76 Suture 76 Enteroexclusion 77 Enterostomy, Jejunostomy, Ileos- tomy 78 Surgery of the Appendix 79 Colostomy 81 Appendicostomyand Cecostomy .... 87 .\ppendicostomy 87 Appendicocecostomy 89 Cecostomy 89 Cecostomy with an Arrangement for Irrigating both the Small Intestine and Colon.. 90 Enterocolonic Irrigator 92 Indications for Direct Bowel Treatment 93 Colectomy 94 Cecectomy 95 Sigmoidectomy 96 Surgical Affections of the Pancreas . . 96 .'\cute Pancreatitis 96 Cancer 98 Cvsts 98 Calculi 98 Pancreatotomy 99 (yii) Vlll COxNTENTS. PAGE Abdomen, Surgery of, Surgical Affec- tions of the Pancreas (cuutunicd) . Pancreatectomy 99 Pancreaticotomy 99 Simple Pancreaticotomy 99 Transduodenal Pancreaticotomy. . 100 Pancreaticostomy and Pancreatico- enterostomy 100 Surgical Affections of the Spleen 100 Abscess 1^ Cysts 00 Splenomegaly 100 Floating Spleen 100 Neoplasms 101 Typical Operations of the Spleen 101 Splenectomy 101 Surgical Diseases of the Liver and Biliary Passages 102 Abscess of the Liver 102 Subphrenic Abscess 103 Cysts of the Liver 103 Neoplasms 103 Cirrhosis 103 Hepatoptosis 103 Cholelithiasis 103 Cholecystitis 104 Obliteration of Bile-passages from Without 104 Tvpical Operations on Biliary Passages and Liver 104 Simple Cystotomy 105 Cystostomy with Drainage 105 Cystectomy 105 Technique 106 Choledochotomy 108 Cholecystenterostomy 110 Excision of Liver; Hepatectomy ... 110 Abdominal Injuries Ill Contusion of the Abdomen Ill Symptoms Ill Diagnosis 114 Lesions of the Intestinal Tract .. 114 Lesions of the Stomach 116 Lesions of the Liver 118 Lesions of the Gall-bladder and Biliary Ducts 119 Lesions of the Spleen 119 Lesions of the Kidneys 120 Prognosis 122 Treatment 123 Shock 123 Reaction 124 Intestines 126 Stomach 126 Liver 126 Spleen 127 Kidney 128 Bladder •. . 129 Wounds of the Abdomen 131 Non-penetrating Wounds 131 Treatment 132 Penetrating Wounds 133 Symptoms 133 Diagnosis 134 Intestines 134 Stomach 135 Liver 136 PAGE Abdominal Injuries, Wounds of the Ab- domen, Penetrating Wounds, Diagnosis {continued) . Spleen 137 Kidneys 137 Bladder 138 Prognosis 140 Intestines 142 Stomach 142 Liver 143 Spleen 143 Kidneys 143 Bladder 144 Treatment 144 Hemorrhage 149 Perforation 152 After-treatjncnt 154 Abortion 154 Delinition 154 Symptoms 1 56 Dangers 159 Etiology and Pathogenesis 160 Maternal Causes 160 Paternal and Fetal Causes 164 Prognosis 164 Treatment 164 Treatment of Threatened Abortion. 164 Treatment of Inevitable Abortion . . 165 Treatment of Incomplete Abortion. 171 Sepsis with Incomplete Abortion. 172 Treatment of Criminal Abortion . . 174 Treatment of Patient with "Abort- ing Habit" 174 Aberrant Forms 174 Missed Abortion 174 Mole 175 Hydatiform Mole 175 Chorioepithelioma 176 Induced Abortion 176 Indications 177 Methods of Inducing Abortion 180 Abortion. Tubal 182 Definition 182 Symptoms 182 Complications 187 Etiology and Pathogenesis 188 Treatment 191 Abscess 196 Definition 196 Varieties 196 EtiologA' 196 Pathofo'g}' 196 Location (Organ or Tissue In- volved) 196 Acute, or Warm 197 Symptoms 197 Etiology 198 Pathology 198 Differential Diagnosis 200 Prognosis 200 Treatment 200 General Measures 200 Surgical Measures 205 Cold, or Tuberculous 207 Symptoms 207 Pathology 207 Differential Diagnosis 208 CONTEXTS. IX PAGE Abscess, Cold, or Tuberculous (con- tinued). Prognosis 208 Surgical Treatment 208 Aspiration and Injections 210 A. C. E. Mixture. See Chloroform. Acetanilide 210 Properties 210 Dose 210 Modes of Administration 211 Incompatibles 212 Contraindications 212 Physiological Action 213 Untoward Effects and Acute Poison- ing 214 Treatment of Acute Acetanilide Poi- soning 217 Chronic Acetanilide Poisoning 218 Treatment of Chronic Acetanilide Poisoning 218 Applied Therapeutics of Acetanilide . . 219 Local Uses 220 Acetic Acid 221 Properties 221 Uses and Dose 221 Physiological Action 221 Acetic Acic^ Poisoning 222 Treatment of Acetic Acid Poison- ing 222 Therapeutics 223 Acetonemia 224 Diagnosis 224 Etiolog>'^ 225 Treatment 225 Acetonuria 226 Physiological and Pathological Excre- tion of Acetone 226 Origin and Pathological Significance of Acetone. Diacetic Acid, and Oxybutyric Acid 228 Preliminary Tests for Acetone 231 Definite Tests for Acetone 233 Acetozone 237 Modes of Administration 237 Therapeutics- 237 Acetparamidosalol. See Salophen. Acetphenetidin 237 Properties 237 Dose 238 Modes of Administration 238 Incompatibilities 238 Contraindications 238 Physiological Action 238 Untoward Effects and Poisoning .... 240 Treatment of Acute Poisoning .... 241 Chronic Poisoning 241 Treatment of Chronic Poisoning . . . 242 Therapeutics 242 Acetylene 244 Acetylene Poisoning 244 Treatment of Acet\-lene Poisoning . . 245 Aciditv of the Gastric Contents, Tests for 245 Acidosis. See Autointoxication. Acne ' 248 Definition 248 Symptoms 248 PAGE Acne {continued^. Varieties 249 Etiology 250 Pathology 251 Diagnosis 252 Treatment 252 General Treatment 252 Local Treatment 253 Acne Rosacea 258 Definition 258 Symptoms 258 Etiolog\^ 259 Patholo'gy 259 Diagnosis 260 Prognosis 260 Treatment 260 Acne Vaccine. See Bacterial Vaccines. Acoin 263 Aconite 263 Preparations and Dose 263 Modes of Administration 264 Local Use 264 Incompatibilities 265 Contraindications 265 Physiological Action 265 Mode of Elimination 266 Aconite Poisoning 266 Treatment of Aconite Poisoning . . . 267 Therapeutics 270 Acrocyanosis. See Vascular System, Disorders of, under Acro- paresthesia. Acromegaly : Pierre Marie's Disease . . 273 Definition 273 Symptomatology 273 The Hypophyseal Syndrome 277 Course and Duration 292 Prognosis 294 Diagnosis 294 Pathology 296 Pathogenesis 302 Treatment 305 Actinomycosis 311 Definition 311 Symptoms 311 Diagnosis 314 Etiology 315 Patholo'gy 316 Inoculation 317 Prognosis 318 Treatment 319 Actol 321 Therapeutics 321 Acupuncture 321 Technique 321 Acute Rhinitis, or Acute Coryza 322 Sj-mptomatology 322 Diagnosis 323 Etiology 324 Pathology 326 Prognosis 327 Treatment ^27 Addison's Disease 332 Symptoms 332 Pathogenesis 338 Diagnosis 344 Treatment 346 X CONTENTS. PAGE Adenitis 350 Definition 350 Varieties 350 Acute Adenitis 350 Symptoms 350 Diagnosis 351 Etiology 352 Pathology 353 Prognosis ; 354 Treatment 354 Chronic Adenitis 355 Symptoms 355 1. General Tuberculous Adenitis. 2. Local Tuberculous Adenitis.. 357 Diagnosis 358 Etiology 359 Pathology 360 Prognosis 361 Treatment 362 Adenoid Vegetations 366 Definition 366 Symptoms and Diagnosis 367 Etiology 371 Pathology ^72> Prognosis 2)7Z Treatment 375 After-treatment 387 Adiposis. See Obesity. Adiposis Dolorosa; Dercum's Disease .. 388 Definition 388 Symptoms and Course 389 Etiology 397 Pathology 399 Diagnosis 404 Prognosis 405 Treatment 405 Adipositas Cerebralis. See Obesity and Acromegaly. Adonis Vernalis 407 Dose 408 Physiological Action 408 Incompatibilities 409 Contraindications 409 Therapeutics : 409 Adrenalin. See Animal Extracts: Adrenals. Adrenals, Diseases of the 410 The Adrenal Secretion in Pulmonary and Tissue Oxidation . . .". 410 The Adrenal Secretion in Immunity.. 411 Classification 412 Terminal Hypoadrenia 413 Definition 413 Pathogenesis and Symptomatology. 413 Pathology ' . 416 Treatment 417 Acute Hyperadrenia and Adrenal Hemorrhage 420 Definition 420 Symptomatology and Pathogenesis. 421 Etiology 424 Pathology 425 Treatment 428 Hemorrhagic Pseudocysts of the Adrenals 429 Symptoms 429 Diagnosis 430 PAGE Adrenals, Diseases of the. Hemorrhagic Pseudocysts of the Adrenals {con- tinued). Etiology 431 Pathology 431 Prognosis 431 Treatment 432 Functional Hypoadrenia 432 Definition 432 Symptomatology and Pathogenesis. 432 Prophylaxis and Treatment 437 Progressive Hypoadrenia 442 Cancer of the Adrenals 443 Varieties 443 Symptoms 443 Diagnosis 445 Treatment 446 Hypernephroma 446 Symptomatology 447 Malignant Hypernephroma of the Adrenals 448 Hypernephroma of the Kidney 450 Symptomatology 450 Diagnosis 452 Pathology 453 Prognosis 454 Treatment 455 Adrin. See Animal Extracts : .\drcnals. Agalactia. See Mammary Gland. Agar-.\gar '. 456 Agaricin 456 Dose 457 Physiological Action 457 Therapeutics 457 Agglutination Test 458 Agoraphobia 460 Agurin 460 Modes of Administration 460 Therapeutics 460 Ainhum 460 Definition 460 Symptoms 460 Etiology 461 Pathology 461 Treatment 462 Airol 462 Modes of Administration 462 Physiological Action 462 Therapeutics 462 Albargin 462 Therapeutics 463 Albuminuria 463 Definition 463 Physiological Albuminuria 463 Physiological Cyclical, Orthostatic. and Orthotic Albuminuria . . 467 Pathological Albuminuria 470 Tests 473 Treatment 482 Albumosuria 483 Alcohol 484 Preparations and Dose 484 Modes of Administration 485 Contraindications 488 Physiological Action 489 Therapeutics 500 CONTEXTS. XI PAGE Alcoholism, or Alcohol Inebriety 511 Definition 511 Toxicity of the Alcohols 512 Varieties 513 Acute Alcoholism 513 Definition 513 Symptoms 513 Differential Diagnosis 515 Patholog}' 517 Treatment 518 Chronic Alcoholism 520 Definition 520 Sj'mptoms 520 Diagnosis 523 Pathology 525 Prognosis 525 Treatment 526 Acute Alcoholic Delirium, or De- lirium Tremens 533 Symptoms 533 Diagnosis 534 Pathology- 534 Prognosis 535 Treatment 535 Acute Alcoholic Mania (Mania a Potu) 539 Symptoms 539 Differential Diagnosis 539 Etiology and Pathology 539 Prognosis 540 Treatment 540 Aleppo Boil. See Oriental Sore. Aloes 540 Properties and Constituents . . 540 Dose and Preparations 541 Modes of .\dministration 541 Incompatibles 542 Contraindications 542 Physiological Action 542 Untoward Effects 543 Therapeutic Uses 543 Alopecia 544 Definition 544 Congenital-Alopecia 544 Senile Alopecia 545 Premature Alopecia 545 Alopecia Seborrhoeica 546 EtioIog>' and Pathology^ 547 Prognosis 548 Treatment 548 Alopecia Areata 551 Definition 551 Symptom.s ^51 Etiology 552 Pathology 554 Prognosis 554 Treatment 554 Alsol. See Aluminum : .\luminum Ace- totartrate. Alum : 556 Dose 556 Modes of Administration 556 Incompatibles 557 Contraindications 557 Physiological .Action 557 Untoward Effects and Poisoning 557 Therapeutic Uses 558 P.\GE Aluminum 560 Aluminum Hydroxide 561 Aluminum Sulphate 561 Aluminum Acetate 561 Aluminum Acetotartrate 562 Aluminum Boroformate 563 Aluminum Borotannate 563 Aluminum Borotartrate 563 Aluminum Carbonate 563 Aluminum Chloride 564 Aluminum Phenolsulphonate 564 Aluminim Salicylate 564 Aluminum Silicate 564 Alumnol 5(>4 Mode of Employment 564 Therapeutic Uses 564 Alypin 566 Untoward Effects 566 Alzheimer's Disease 566 Amaurosis 567 Definition 567 Amaurosis in Brain Disease 567 Amaurosis in Nephritis 567 Amaurosis in Hysteria 568 Amaurosis in Spinal Disease 568 Amaurosis following Hemorrhage. 569 Amaurosis in Pregnancy 569 Amaurosis from Fracture of the Skull 570 Congenital and Hereditary Amau- rosis 570 Amblyopia 572 Definition 572 Toxic Amblyopia ....'. 572 Loss of Vision 572 Central Scotoma 573 Papilla Changes 573 Acute Poisoning 573 Amblyopia from Intracranial Causes. 573 Hysterical Amblyopia 574 Simulated Amblyopia 574 Amblyopia Exanopsia 575 From Congenital Defects 575 From Defects of Refraction .... 575 Amblyopia from Exhaustion 576 Amenorrhea 576 Definition 576 Varieties 576 Symptoms 576 EtiolO'g\' ,....• 577 Patholog3.r 579 Diagnosis 579 Prognosis •^79 Treatment 579 Amidoacetphenetidin Hydrochloride. See Phenocoll Hydrochloride. Aminoform. See Hexamethylenamine. Ammonia 581 Properties 581 Preparations and Dose 582 Modes of -Administration 582 Incompatibles 583 Contraindications 583 Physiological Action 583 Local Effects ^ 583 Effects on Internal Use 583 Toxicology 584 Xll COXTENTS. PAGE Ammonia, Toxicology- (continued). Treatment of Ammonia Poisoning . 585 Applied Therapeutics of Ammonia . . 585 Ammonium 587 Physiological Action 588 Ammonium Acet te 589 Mode of Administration 589 Incompatibles 589 Physiological Action 589 Therapeutics 590 Ammonium Carbonate 590 Modes of Administration 591 Incompatibles 591 Physiological Action 591 Toxicology 592 Therapeutics 592 Ammonium Chloride 592 Modes of Administration 593 Incompatibles 593 Physiological Action 599 Therapeutics 594 Ammonium Ichthyol Group. See Ichthyol. Amnesia 596 Amputations and Resections. See Resec- tions, Amputations, etc. Amy] Nitrite. See Nitrites. Amylene Chloral. See Dormiol. Amylene Hydrate 597 Dose and Modes of Administration . . 597 Physiological Action 597 Untoward Effects ; Poisoning 598 Therapeutic Uses 598 Amyloform 599 Physiological ^ vction 599 Therapeutic Uses 599 Amyl Valerate 600 Physiological Action 600 Therapeutic Uses 600 Analgen 600 Therapeutic Uses 601 Symptoms 601 Diagnosis and Pathogenesis 603 Etiology and Pathology 604 Prophylaxis 605 Treatment of Anaphylactic Reaction . . 607 Anemia, Pernicious Progressive 608 Definition 608 Symptomatology 608 Blood Examination 610 Pathology 613 Diagnosis 616 Benign Anemia 616 Chlorosis 616 Leukemia 616 Pseudoleukemia 616 Gastric Cancer 616 Etiology 617 Prognosis 619 Treatment 620 Anemia, _ Secondary, or Symptomatic . . 626 Definition 526 Types of Secondary Anemia 627 Posthemorrhagic Anemias 627 Infectious and Toxic x'\nemias 627 Trophic Anemias 628 PAGE Anemia. Secondary or Symptomatic (con- tinued). Pathology 629 Symptomatology 632 Diagnosis 634 Prognosis 636 Treatment 636 Anencephaly 641 Anesin. See Chloretone. Anesthesia 642 Choice of Anesthetics 642 Ethyl Chloride 642 Chloroform 642 Nitrous Oxide 642 Ether 642 Ether-Oxygen 642 Oil-ether Colonic Anesthesia 643 Nitrous Oxide Gas 643 Preliminary Narcotics (43 Miscellaneous Factors 644 Fright 644 Breathing Test to Ascertain Condi- tion of Heart Muscle 644 Pre-anesthetic Diet 644 Self -anesthesia in Field 644 Heating of Anesthetic 644 Trendelenburg Position as Source of Danger 645 Shock During General Anesthesia ..645 Post-anest'ietic Intoxicatio.i 645 Post-anesthetic Vomiting 645 Effects on the Adrenals of Anes- thetics 646 Untoward Effects of Adrenalin .... 646 After-efYects on Nervous System . . 646 Narcoanesthesia 647 Comparative Merits of Various Local Anesthetics 647 Anesthesia Acidosis 648 Prophylaxis 648 Anesthesin 649 Physiological Action 649 Therapeutic Uses 649 Aneurism 650 Definition 650 Varieties 650 Etiology 651 Pathology 653 Symptoms 655 Course 659 Differential Diagnosis 659 Treatment 660 Arteriovenous Aneurism 668 Aneurismal Varix 668 Varicose Aneurism 668 Symptoms 668 Treatment 669 Conditions Related to Aneurisms 670 Angina Ludovici. See Pharynx and Tonsils, Diseases of. Angina Pectoris 670 Definition 670 Symptoms 670 Diagnosis 672 Intercostal Neuralgia 673 CONTENTS. xiu PAGE Angina Pectoris, Diagnosis (continued). Gastralgia ^^I'^ Cardiac Asthma 673 '"Pseudoangina" (^73 Hysteria 674 Syphilis 674 Tobacco, Tea, etc 674 Etiology 6/5 Pathology 676 Prognosis 680 Treatment 680 Angiomata. See Blood-vessels, Tumors of. Angioneurotic Edema. See Ascites and Edema. Anhalonium Lewinii 685 Preparations and Dose 686 Physiological Action 686 Therapeutic Uses 687 Anhidrosis, or Anidrosis. See Sweat Glands, Diseases of. Animal Extracts, or Organotherapy 687 Thyroid Gland Organotherapy 689 Physiological Action 690 Thyroxin 693 Antitoxic Flection 693 The Active Principle of Thyroid . . 696 Preparations and Dose 697 Untoward Effects and Their Preven- tion 698 Treatment of Thyroid Poisoning . . . 698 Therapeutics 699 Hypothyroidia, or Hypothyroid- ism 700 Hyperthyroidia, or H>-perthyroid- ism 704 Untoward Effects 706 Cretinism 708 Myxedema 715 Obesity 719 Miscellaneous Disorders 722 Acromegaly 722 Arthritis, Chronic Rheumatoid.. 723 Cancer 726 Cutaneous Disorders 729 Exophthalmic Goiter or Graves's Disease 731 Hemophilia 731 Incontinence of Urine 731 Infectious Diseases 731 Insanity 732 Lactation 723 Middle-ear Disorders 733 Nervous Disorders 733 Epilepsy 733 Eclampsia 734 Migraine 735 Asthma 735 Tetanus 735 Osseous Disorders 735 Rheumatism, Chronic Progress- ive 736 Uterine Disorders 736 Summary 737 Parathyroid Organotherapy 737 P.\GE Animal Extracts, Parathyroid Organo- therapy {continued) . Therapeutics 738 Adrenal or Suprarenal Organotherapy 740 Physiological Action 742 Preparations and Dose 745 Contraindications 747 Untoward Effects 747 Therapeutics 750 Addison's Disease 750 Shock, Collapse, and Surgical Dis- eases 751 Toxemias and Bacterial Infec- tions 753 Postoperative Intestinal Atony . . 756 Miscellaneous Disorders 757 Hemorrhage 757 Asthenic Cardiac Disorders with Dilatation 757 Asthma 758 Effusions 758 Disorders of Pregnancy and Parturition 758 Cancer 758 Osteomalacia 759 Local Uses 760 Hemorrhage 760 Hemorrhoids 761 Neuralgia, Sciatica, and Neu- ritis 761 Cutaneous Disorders 761 Pituitary Organotherapy 761 Preparations and Dose 763 Therapeutics 764 Acromegaly 7(A Cardiac Disorders 764 Obstetrics 766 Infectious Diseases 769 Exophthalmic Goiter 770 Nervous and Mental Diseases and Myopathies 770 Stunted Growth and Imbecility . . 771 Intestinal Paresis 772 Orchitic or Testicular Organotherapy ; Spermin 773 Therapeutics 775 Ovarian Organotherapy ■ 775 Preparations and Doses 777 Therapeutics 777 Natural and Artificial Menopause. 777 Corpus Luteum Organotherajjy 77^ Preparations and Doses 779 Therapeutics 779 Kidney Organotherapy 783 Therapeutics and Dose 783 Thymus Organotherapy 784 Therapeutics 785 Diseases of the Thyroid 785 Rachitis, or Rickets 785 Bone-Marrow Organotherapy 786 Brain and Nerve Substance Organo- therapy 786 Mammary Gland Organotherapy .... 787 Spleen Organotherapy 788 Hepatic Organotherapy 788 Bile. Bile-Salts, and BHiary Extracts.. 789 SAJOUS'S ANALYTIC CYCLOPEDIA of PRACTICAL MEDICINE ABDOMEN, SURGERY OF — Abdominal surgery in its wide sense includes a great variety of operative procedures whio+i are based upon the same general principles as the ones which are included in this article, but which have been left to contributors in the other departments : all of the external hernias, a good part of renal surgery, the surgery of the abdominal walls, and all of the pelvic surgery of the female. This article takes account of that part of abdominal surgery which in- cludes hollow and solid viscera, the former comprising the various parts of the alimentary tube between the diaphragm and the brim of the pelvis, all biliary and pancreatic ducts and the gall-bladder. The solid viscera belonging to this series of articles comprise the liver, spleen and pan- creas only. There is a general sameness of the alimentary canal in these various parts which leads to more or less correspondence between operations done at the different levels of this tract. Operations of the biliarv' ducts and gall-bladder also have many points in common, and they resemble in a way the operative resources that are emplo^'ed for the genitourinary passages. We propose to consider the spe- cial features of abdominal surgery in two ways : first, as a series of typical operations which are intended to cor- rect certain diseased states, and then from the other direction as a series of diseased states to be relieved by operative procedures of various kinds. It seems therefore of advantage to consider the typical operations for the stomach, small and large intestines and biliary passages as operations which are in a way applicable to all surgical conditions of these organs. Surgical diseases of the peritoneum, appendix, liver, spleen and pancreas require separate consideration in detail, be- cause of the relative absence of typi- cal operations, making the treatment more or less individualized for each case. THE FOURTH ERA IN SUR- GERY.— In abdominal surgery we have perhaps the best field for object lessons relative to the new fourth or physiologic era in surgery. The first era in surger}' was the heroic, under which practically no abdominal sur- gery was done. In the second or anatomic era of surgery, abdominal 1— t ABDOMEN, SURGERY OF (MORRIS). operations were in general so danger- ous that few were attempted, except- ing in cases of great emergency, and usually with a fatal ending. The third or pathologic era of surgery was based upon the studies of Pasteur and of Lister. Aside from its technique of preventing the development of bac- teria in wounds, it included the idea of removing all products of infection with painstaking care. Notwithstanding the injury that was done to patients by surgeons carrying out the principles of this era, abdominal surgery made its first great advances. Detailed attention was given to the deliberate disposal of products of infection found within the peritoneal cavity, and little or no at- tention was paid to the natural re- sistance forces contained within the patient himself. There was an enor- mous waste of such forces, in fact, in our abdominal surgery of the patho- logic era. The entirely modern or physiologic era is based upon the studies of Metchnikofif and Wright, and includes the principal idea of allowing the patient to retain his natural forces in such a way as to gain control of infections. MetchnikofF and his fol- lowers taught us that certain cells of the blood and lymph circulatory sys- tems not only disposed of bacteria daily under normal conditions, but that these cells were increased in number rapidly to meet emergen- cies of infection. These investigators showed also that bacteria were de- stroyed by certain fixed body cells. Wright and his followers showed fur- ther that, in the presence of an infec- tion, several kinds of antibodies were elaborated in the animal economy, and these antibodies lent their aid in removing infections and in destroy- ing certain toxins that were produced by bacteria. The principles of this fourth or physiologic era of surgery brought us face to face with the problem of operating in such a way as to leave the patient in the very best condition for managing infec- tions himself with his own phagocytes and antibodies, and led to a revolu- tion in methods, forcing us to drop out of our technique such parts of the system of the third or pathologic era as interfered with the ability of the patient to produce phagocytes and antibodies. For instance, a prolonged and painstaking operation for removing all of the pus from the peritoneal cavity so shocked the great vaso- motor centers of the patient that they were palsied, and unable promptly to take up the work of conducting the manufacture of phagocytes and anti- bodies, with which the patient him- self could dispose of the products of infection much better than the sur- geon could do it in his crude mechani- cal way. Unnecessarily prolonged operations acted in precisely the same way; and where we had thought best to expend a half-hour in carrying out the theories of the pathologic era in surgery, we may now expend five minutes under the principles of the physiologic era. Experimentation has shown that shock is produced more readily by manipulation of the abdominal viscera than by gross in- juries, when animals are fully anesthetized, especially when the anesthetic used is chloroform. The parietal peritoneum and mesenteries are especially sensitive. These facts emphasized some years ago by Mum- mery and Symes ar now fully recognized. Editors. ABDOMEN, SURGERY OF (MORRIS). 3 A long period of anesthesia was organs, spinal anesthesia according to commonly required for thorough work the Jonnesco method is desirable, under the principles of the third era, Preoperative intestinal asepsis can but we now know, from our experi- only be approximated, but for most ments upon animals, that individuals practical purposes a good purgative profoundly under the influence of given within twenty-four hours of alcohol, or of ether or of chloroform, operation will suffice. If the stomach temporarily lose resistance to infec- itself is to be operated upon, further tions, and some acute infections which steps in the direction of asepsis are would not gain headway under a few required, and we wash the stomach mJnutes of anesthesia may seize the out very thoroughly with saturated opportunity to gain ascendancy if the boric acid solution just in advance of anesthesia is prolonged for an hour or operation. This is done most comfort- two. Bulky or complicated drainage ably, as a rule, after the patient is apparatus, acting as a foreign body, under the influence of the anesthetic, further produces derangement of func- and by means of the common siphon tion of the vasomotors in such a way tube. After the alimentary tract has as to prevent the^^^atient from manu- been cleansed by purgatives, it is im- facturing his phagocytes and anti- portant to give only the simplest arti- bodies. We are just entering, then, cles of food and drink in advance of the era in which the greatest degree the operation, 'but we must avoid hav- of success is to follov/ our opera- ing a patient abstain in such a way tive procedures within the abdominal as to become unduly weakened. Pa- cavity, tients who are accustomed to dieting ANTEOPERATIVE MANAGE- may sometimes be placed on special MENT. — Aside from the general prin- diet to advantage for a few days in ciples which govern the preparation advance of operation, but the physical of a patient for any major operation, effect of placing a patient on diet for certain special requirements are indi- any length of time is apt to be such cated which les_sen the operative risk, as to counteract any good effect, and the tendency to postoperative Special stress has of late been laid complications in abdominal surgery. on carbohydrate star\'ation as a cause Postoperative pneumonia, for in- of acidosis. It is important that an stance, will occur less often if we excess of ketone substances, acetone, make careful choice of the anesthetic diacetic, and oxybutyric acids (aceto- for any given case, and if we make nemia, q.v.), sometimes with increased this period of anesthesia as short as ammonia elimination, should be looked possible, on account of the known for by laboratory tests prior to tendency of some acute infections to operation. shoot ahead when the patient is under The expenditure of muscular eti- the influence of ether or chloroform. ergy before, during, and after opera- Some operators will choose nitrous tion entails a deficiency of glycogen oxide and oxygen in cases in which ^^'^ich carbohydrate starvation only ., • , . .• • . 1 T serves to aggravate, and which mani- this pnenomenon is anticipated. In r . •. ir u a ■ -t-u ^,.^h„^n ^ ^ fests Itself by acidosis, with dyspnea, some feeble patients, or patients with tachycardia and acetone breath as main complications of disease of vital phenomena. When acetone or di- ABDOMEN, SURGERY OF (MORRIS). acetic acid is found in the urine in such cases, active treatment is indi- cated. Following Bainbridge's routine preoperative treatment the writer ad- ministers a purgative and for several days milk sugar and also sodium bi- carbonate by mouth and rectum, to reduce the acidity of the urine to nor- mal limits. In marked acidosis, large colonic irrigations of the same salt 6 to 10 quarts — liters — of a solution, 1 dram — 4 Gm. — to the pint — 500 c.c, are given daily, for the same purpose. Burnham (Amer. Med., Nov., 1916). Inability to assimilate carbohydrates is best treated by supplying enough carbohydrate and by the neutraliza- tion of acid products with alkali. Sur- geons must keep their eyes open to the dangers of acidosis. Prolonged starvation is especially harmful in children or those suffering from any form of exhaustion. W. A. Lincoln (Annals of Surg., Ixv, 135, 1917). It is far better to omit the cathar- tic or prepare the patient according to the following plan: Seventy-two hours before operation the bowels are cleared with castor oil. After the cathartic only liquids or food that will leave very little residue is permitted. In rectal operations, the evening before the operation the patient is given a high enema of nor- mal saline solution, and 2 hours be- fore operation a copious low enema of warm saturated boric acid solution. Fansler (Jour.-Lancet, Nov., 1920). Preoperative Purgation.— This measure has recently been condemned by a num- ber of prominent surgeons, who found its omission beneficial owing mainly to the fact that a purged bowel is often distended with gas and decidedly congested. Sajous has pointed out that purgatives sweep from the intestinal canal a product termed "secretion," by Starling, which not only serves to liberate and activate the pan- creatic enzymes, but also to promote the production of bile and succus entericus. Normally, after about 24 hours this tem- porary deficiency adjusts itself; if, how- ever, an operation is performed, this re- adjustment is retarded in proportion with the shock involved. Again, Sajous hav- ing shown that the intestinal enzymes are bactericidal and antitoxic, their elimination by purgatives tends to favor autointoxica- tion and fermentation. In general a short period, of rest in bed before an operation is of advan- tag-e, but if this time extends beyond twenty-four hours, excepting for pa- tients who are already in bed with some severe abdominal complication, the apprehension and introspection of the patient with a negative imagina- tion in advance of operative proced- ures may be disastrous, and has even gone to the point of allowing the patient to develop suicidal impulse. For patients who are not already in bed from necessity, the author pre- fers to have as short a period of prep- aration as expediency would suggest, not more than twenty-four hours as a rule. There are many instances in which the patient needs special medical treatment in advance of oper- ation, because of some defect of the heart, lungs, or kidneys, but under such circumstances with most pa- tients it is best not to tell them of the date set. for operation far in advance, up to which they are to be led. The prognosis of preoperative shock is materially improved if an hour or two is allowed for resuscita- tion prior to operation, during which saline solution is given subcutane- ously or by vein, warmth applied, an opiate injected, and camphor in oil given subcutaneously if a stimulant is required. Prior to operation it is well to give omnopon and scopola- mine. The best anesthetic was found to be warm ether and oxygen. Lock- wood, Kennedy, Macfie and Charles (Brit. Med. Jour., Mar. 10, 1917). Anteoperative narcosis is undesir- able for one chief reason shown by Cantacuzene in his experiments with animals subjected to the influence of opium after infection. This author ABDOMEN, SURGERY OF (MORRIS). showed that narcotized animals rapidly succumbed at the time when another series subjected to the same infection, but not narcotized, were meeting the infection. Arrangements should be made be- forehand for maintaining the animal warmth of the patient with woolen garments or blankets, and it is best to have a good circulation of air in the operating room. In an over- heated operating room witii closed windows and doors the surgeon him- self may be extremely uncomfortable, and feeling the need for oxygen, and we assume that the patient at the same time sufifers the same depressing influence in addhion to the shock of the operation. Experiments with animals have shown that the perito- neum is not injured by exposure to air currents and to low temperature as much as it is injured by contact with gauze, antiseptic solutions, or by rough handling. The author believes that the temperature and air circulation of the room most agreeable to ', call for a surgical consultation, which in a large majoritj^ of cases will lead to an exploratorj' operation. 2. The finding of a movable tumor in the pj'loric end of the stomach cannot be overestimated as to its surgical sig- nihcance. Gastric cancer by itself does not give, he is convinced, char- acteristic symptoms during the cur- able stage. But if it is situated in the pjioric end of the stomach mechan- ical conditions are early induced which afford most valuable informa- tion. An effort should alwaj'S be made to remove the lymphatic area, whether diseased or not. It must be removed before the Ij-mphatics are infected. Prophylaxis of gastric can- cer can be aided by the excision of calloused gastric ulcers, which are its origin in 70 per cent. A typical re- section necessitates the removal of all that part of the stomach lying to the right of a line dropped vertically from the cardiac orifice, though in some cases more of the fundus must be removed on account of the direct extension of the disease. As a gen- eral rule, it will be most conxenient to make the separation of the super- ior border of the stomach first, be- ginning the operation by (a) ligation of the superior pyloric vessel, (h) the gastric, {c) th.;- left gastroepiploic, {d) 56 ABDOMEN, SURGERY OF (MORRIS). the gastroduodenal vessels. As each vessel is secured, the glandular sep- aration is effected. In doing the an- terior gastrojejunostomy he usually follows the method of Hartmann. i.e., the two-row suture method with slight modifications. Generally speak- ing, the Kocher method of joining the jejunum to the stomach is not so satisfactory as the Billroth No. 2 method, i.e., closing both the end of the duodenum and the stomach and making an independent gastrojejunos- tomy. When the patient is in good condition the oi)eration has an opera- tive mortality of under 5 per cent. In advanced cases, the resection is worth the risk, considering the short lease of life of patients left without it. W. J. Mayo (Jour. Amer. Med. Assoc, May 14, 1910). In the method of gastrectomy de- scribed by the writer, a crushing in- strument consisting of 3 sets of blades is used. The crushed tissue is cut across. An over-and-over suture is used; after removal of the pro.xi- mal crusher an invaginating suture, beginning at the center and working out to the ends, is inserted. The distal portion of the stomach is raised with one section of crusher on the cut end. The duodenum is sectioned in one of several ways. A gastro- enterostomy is finally done in the usual manner. T. De Martel (Amer. Jour. Surg., xxxv, 227, 1921). Complete Gastrectomy. — This oper- ation, including subtotal gastrectomy, is now practicable as a method, and has radically cured perhaps a ver}' few individuals of cancer, but is seldom attempted, the operative mor- tality being very great and cases suit- able for such intervention seldom recognized in time. Removal of the stomach is not a difficult operation at all, but search for and removal of lymph-nodes must be very thorough. The removal is followed by an end- to-end anastomosis made between the duodenum and esophagus, or the cut end of the former may . closed and the esophagus implanted into the jejunum. The author has found it much easier to do the work if a small part of the cardiac end of the stomach is allowed to remain. SURGICAL DISEASES OF THE PERITONEUM.— Septic Peritonitis. — This condition being in tiie great majority of cases secondary to some suj)purative process either within or without the peritoneal cavity, the treatment cannot l)e considered inde- pendently of that of the primary condition, which consists fundament- ally of incision and drainage of or removal of the pyogenic focus. The conditions likely to give rise to peri- tonitis are separately mentioned. If the focus is outside the peritoneal cavity, the latter need not necessarily be opened, because the peritoneum rapidly guards itself by hyperleuco- cytosis after a focus of infection is cared for. If tlie focus is in the peri- toneal cavity, it may or may not be advisable to treat the peritoneum actively. If the peritonitis coines from an intestinal perforation an enterorrhaphy may be required, but it is often safer to make temporary ■drainage, and fistulae following have a tendency to close spontaneously. Other cases may require excision, as when a portion of the gut is gangren- ous. In many cases, however, posture and drainage alone are indicated, and any unnecessary handling of tiie peri- toneum is to be deprecated. Only when drainage cannot offer a pros- pect of self-limitation of the process is a thorough cleansing of the peri- toneum indicated, and this is best accomplished by flushing with hot saline solution tli rough short incision, and the glass tube. ABDOMEN, SURGERY OF (MORRIS). 57 The mortality from peritonitis has been much reduced by Murphy's treatment, which consists in making a small opening in the abdomen, doing such operation at the point of origin of the peritonitis as is required, the introduction of a large drain- age-tube into the pelvis, placing the patient in a sitting posture of 35 to 40 degrees, and the administration of salt solution every two hours by rectum. An important feature is to avoid handling the intestines or peritoneum more than is absolutely necessary. It was Murph}-'s protest against general irrigation of the abdomen, showing that the higher mortality rested with those who used it, that tirst attracted the atten- tion of surgeons to R. E. Kelly. His first paper dealt with 5 cases (including 1 typhoid case) without a death, was fol- lowed in October, 1906, with 28 cases with 1 death, and up to a later paper included 48 consecutive cases with only 2 deaths. These are astounding results when com- pared w-ith the prior 50 per cent, mortality at the Mayo clinic. The principles laid down by Murphy were: 1. Operate early. 2. Operate quickly. Murphy gave ten minutes as the average time in which to close the gastric or duodenal opening, or to remove the offending appendix or tubes. 3. The anes- thetic must always be ether, if the patient can stand it; if not, then a local. anesthetic. Stiles's work has shown how dangerous chloroform is in acute suppurative condi- tions, in the production and retention of acetone. 4. It is a fatal mistake to mop, wash, or handle the intestine. The peri- toneum is essentially an absorbing surface; carmine granules injected into its cavity are rapidlj' absorbed especially in its upper half, and conveyed b\' the lymph-stream to the general circulation. Organisms similarly do harm bj' the rapid absorption of their toxins in a similar manner. Lymph ii protective, and tends to prevent this absorption. 5. The Fowler position and a suprapubic drain. The object of the Fowler position is to allow the discharges to gravitate toward the pelvis, and away from the danger zone of the diaphragm. The patient, as soon as he has recovered from the anesthetic, is placed in the sitting posture, so that the abdominal cavity is vertical in position, and drainage is insti- tuted bj' placing a large drain in the pelvis through a stab wound above the pubis. This drainage-tube is three-fourths to one inch in diameter, about eight inches long, glass, and goes down to the pouch of Douglas in the female, and the rectovesical in the male. In this position the tube is almost horizontal; and if it is filled with fluid, each excursion of the diaphragm will pump a small quantity of it out into tlie dressings. The hole is now at the most dependent part of the abdominal cavity. 6. Peritonitis treated by the Murphy method Proctoclysis or the absorption of large quantities of saline by the rectum for the first two days after operation. As soon as possible after the operation, a tube having numerous holes in it and one-half inch in diameter is inserted into the rectum for about two to three inches. This is con- nected by means of a rubber tube of the same diameter with a container suspended from four to twelve inches above the plane of the patient's couch, and the whole is filled with warm saline. By means of this head of water (it need only be four to six inches in height, as a rule) saline gradually trickles into the rectum at about the rate of three-quarters to one pint an hour. The temperature of the saline is kept at ICX)" F. 58 ABDOMEN, SURGERY OF (MORRIS). and should never reach 106° P., or it will not be retained. Editors. Description of a scheme of treat- ment for peritonitis based on experi- ence in 13,145 laparotomies. By this plan the mortality in all abdominal operations was decreased 33Vs per cent., and in acute appendicitis alone, 67.6 per cent.: (1) Nitrous oxide- oxygen anesthesia. (2) Local anes- thesia at site of incision. (3) Ac- curate, clean-cut operation to dimin- ish both infection and shock. (4) Ade- quate drainage. (5) Fowler's position. (6) Vast hot packs over the entire abdomen, spreading well down over the sides. (7) Five per cent, sodium bicarbonate with 5 per cent, glucose by rectal drip, continued as long as it is tolerated. (8) Primary lavage of the stomach, repeated only if in- dicated. (9) From 2500 to 3000 c.c. (5 to 6 pints) of physiological so- dium chloride solution subcutane- ously every 24 hours until the period of danger is past. (10) Morphine hypodermically until the respiratory rate is reduced to from 10 to 14 per minute, and held to this rate until danger is past. The morphine is not useful in a streptococcus peritonitis. G. W. Crile (Jour. Amer. Med. Assoc, Nov. 29, 1919). According to the writer, advancing postabortal peritonitis has a definite symptom complex in the presence of which drainage is necessary and defi- nitely lowers the mortality. The patient is placed in the high Fowler position; one or more icebags are applied to the abdomen, and a proc- toclysis by the Harris method of glucose-sodium-bicarbonate solution is begun. The pain is relieved by routine morphinization, small doses being given hypodermically at regu- lar intervals. If the patient's resist- ance is capable of taking care of the peritoneal invasion, in from 12 to 20 hours there will be a definite reces- sion in the severity of the symptoms and a fall in the polymorphonuclear percentage. On the other hand, if resistance is insufficient, or virulence greater than the protective reaction, the pulse, temperature and local ab- dominal symptoms will remain sta- tionary or increase in severity, and the polymorphonuclear percentage will rise. A posterior vaginal in- cision through the fornix will usu- ally liberate a pint or more of thin, flocculent blood-stained serum which on culture returns innumerable strep- tococci. Polak (Amer. Jour. Obstet., Oct., 1920). Report of 22 cases of peritonitis treated by instillations of ether, with 17 recoveries and 5 deaths. Of the former, 9 were in a very desperate condition when operated. The author believes himself justified in recom- mending ether treatment. Neudoerfer (Zentralbl. f. Chir., xlviii, 2, 1921). Twenty-two cases collected from literature, among which enterostomy seemed to be the decisive factor in the recovery in 12 cases. A cone of intestine is drawn up, its base sutured to the skin, and a thread run around it about 2 cm. from the tip. A cath- eter is then worked into a minute opening in the tip and the thread drawn tight, fastening the tip of the cone to the catheter. The latter is then pushed in as far as desired, thus invaginating the cone and protecting the portion of the intestine fastened to the wall from any contact with the bowel contents. Aievoli (Riforma Medica, Apr. 16, 1921). He who operates in a case of acute diffusing peritonitis after the first 36 or 48 hours of the onset of peritoneal inflammation, with no evidence of a localizing point, is, in the majority of cases, not serving the best interests of the patient. In the presence of a circumscribed peritonitis with a definite localizing point of exquisite tenderness, due to an acutely in- flamed, perforating or gangrenous appendix, operation can be undertak-en in the absence of constitutional or other contraindications, provided the proper technique is observed in safe- guarding the peritoneum from con- tamination by the proper disposition of gauze packings. Peritonitis the result of intestinal obstruction, gas- ABDOMEN. SURGERY OF (MORRIS). 59 trie, duodenal, gallbladder, intestinal, or colonic perforation, should be im- mediately operated if the condition can be recognized, which it usually can if the case is seen early. Too thorough operation in peritonitis too often spells death. In peritonitis it is not the inflammation of the peri- toneum that is fatal, but the toxins absorbed. J. B. Deaver (Trans. Phila. Co. Med. Soc; Med. Rec, Apr. 30, 1921). Tuberculous Peritonitis. — In theory the local fucus of disease which has caused an extension of the process to the peritoneum should be excised, whether this is in the intestine, Fallo- pian tube, appendix, or other remov- able tissues. But this is not always practicable, and, furthermore, patients often recover under simple laparot- omy and drainagfe. The author in a series of experiments with animals some years ag^o came to the conclu- sion that this cure of tuberculosis of the peritoneum after opening the peri- toneal cavity was due to the presence of toxins developed from bacteria •which grew in the culture medium of peritoneal exudate exposed by way of the drainage-tube. This was in fact true, and i:he cultures of tubercle bacilli in test-tubes were instantly killed by toxins extracted from such fluid and applied to the cultures. A later theory, however, and one which is borne out by later studies, is that the tubercle bacilli are de- stroyed by phagocytes in the course of the intense hyperleucocytosis which promptly follows opening of the peri- toneal cavity for any purpose. The idea that such hyperleucocytosis proves destructive to the tubercle bacilli is further substantiated by the fact that various substances injected into the peritoneal cavity have proved effective in the same way, and for the destruction of tubercle bacilli in the peritoneum it apparently matters little which method for exciting exag- gerated hyperleucocytosis is chosen, so long as we bring about that phe- nomenon. According to A. K. Stone, operation should only be undertaken when there is some distress from the distention; it is better to wait for a period with the pa- tient at rest and under the same hygienic conditions to which any case of pulmonarj' tuberculosis would naturally be subjected, namely, rest, fresh air, good food, and, later, moderate regulated exercise. If after si.x or eight weeks there is no im- provement in the symptoms, operation should be considered. When once the dis- ease is arrested, whether by operation or hygienic methods of treatment, the pa- tients must be taught to regulate their lives with the same care that they would had their disease been located in the lungs. Laparotomy alone should not be considered a cure, but the disease treated in the light of the patho- logical conditions found in each case. Often, when diagnosed early, the peritonitis is found to be confined to the region of the primary focus, such as the appendix, cecum, and Fallopian tubes. In such cases removal of the entire infected area with its under- lying organ or organs is the rational method of treatment, to be followed by energetic hygienic measures and the administration of tuberculin. Where the disease has become so widespread that it cannot be re- moved surgically, laparotomy is not only not indicated, but may hasten the fatal issue. O. M. Shere (Colo. Med.. June. 1917). Surgeons are still in disagreement as to the operative procedure to be followed, whether simple puncture, simple laparotomy or laparotomy with consecutive peritoneal lavage. Cecherelli attributes vast importance to lavage. According to the author, it may be used in every anatomic variety of tuberculous peritonitis, and is absolutely indicated in the forms in which purulent diffused or circum- 60 ABDOMEN, SURGERY OF (MORRIS). scribed collections accumulate toxic material. Operation is probably in- dicated in all forms except where the tuberculosis involves the lungs or is spread to many viscera or where the general state does not permit it. Ruffo (Riforma Med., June 16, 1917). The writer reports cure in 12 out of 15 cases and material improve- ment of the others by operative treat- ment. Through a median laparotomy he paints the whole accessible peri- toneal surface with official tincture of iodine, loosening up adhesions only as necessary to reach all the surface. The abdominal wall is always sutured at once. Stocker (Corresp.-Blatt f. schweizer Aerzte, June 23, 1917). Disappearance of effusion, when present, may be hastened by moder- ate purgation, diet restriction, and ordinary diuretics. X-ray treatment has benefited some patients. Lapar- otomy is indicated in serous effusion if, after several weeks of conserva- tive treatment, satisfactory progress has not been made. Nitrous oxide oxygen anesthesia should always be used. C. A. Vance (Trans. Ky. State Med. Assoc; Jour. Amer. Med. Assoc, Nov. 1, 1919). In intestinal occlusion due to peri- toneal tuberculosis, both the occlusion and the peritonitis may be treated bj- a laparotomy. An artificial anus is necessary only if the patient's condi- tion is very poor or if it becomes evident that nothing else can be done. Aimes (Rev. de chir., Iviii, 1/7, 1920). The writer deems tuberculous peri- tonitis very amenable to cure in most instances, at least if the abdominal condition is the main factor. Nature can cure tuberculous peritonitis in pure form. Mixed infection destroys tissue, but added toxins are destructive to life as well as to tissue, and are more chronic and difficult to treat or control. If ascites in tuberculous peritonitis adds so enormously to the surface area involved in a tuberculous process and must be overcome by changes in the peritoneum by chang- ing the exudate from serous to fibrin- ous and plastic adhesions before cure occurs, such surgical treatment as will hasten the process is advisable. Death or even ill health rarely comes from obstruction due to the adhe- sions. When acute obstruction de- velops it is due to a single band or the hyperplastic variety without ascites. By removing the focus of disease in tuberculous peritonitis, especiallj- when such a focus involves a tuber- culous mucous membrane, a high per- centage of permanency of cure with a very low primary operative mor- tality is secured. Mayo (Minn. Med., Apr., 1921). Ascites. — We speak of surgical treatment of ascites rather than of cirrhosis of the liver in cases of. the latter disease, because the operation has probably little influence upon the liver itself. Ascites and hydroperi- toneum from whatever cause may be relieved teinporarily by paracentesis. The incidental laparotomy with drainage corrects the condition for the time being-. We have to be par- ticularly careful to guard the peri- toneum against infection in many of these cases, for the reason that the current of lymph is outward from the peritoneum, and it becomes exposed to various bacteria. When the cur- rent is inward, as in normal condi- tions; there is destruction of entering bacteria by the action of blood- and body- cells. Warning against removal of recent tuberculous effusions. .^11 patients operated on for tuberculous peri- tonitis within 2 months of its appar- ent onset have died, in the author's experience with 100 cases.. Only effusions from 3 to 5 months old should be removed. There follows spontaneously a new, curative effu- sion. This is the view now held by many clinicians. Gelpke (Corre- Congenital Cysts of the Mesentery. {H. C. Dearer.) Annals of Surgery. ABDOMEN, SURGERY OF (MORRIS). 61 spond.-Blatt f. schweizer Aerzte, Jan. 12, 1918). Omentopexy or the Talma-Drum- mond operation has for its aim the establishment of adhesions between the omentum and parietal peritoneum. These adhesions become filled with capillary' blood-vessels in time, and the free network of small new vessels constitutes a venous anastomosis around the area of obstructed circu- lation. This work may be done by in- troducing numerous pinpoint sutures, or by pulling- the omentum between the transversalis fascia and the pos- terior sheath of the rectus muscle, and'fixing it there. In addition to establishing a new circulation by the roundabout way of adhesions of the omentum, it is well to scarify the cephalad surface of the liver and the corresponding perito- neum of the diaphragm. This may be done very rapidly by the use of a nailbrush with the bristles cut very short. The peritoneum which has been denuded of its endothelium in this way throws out abundant lymph and makes extensive adhesions, which later are filled witli new capillaries. The operation seldom accomplishes the object for which it is intended in a satisfactory way, because it is commonly used as a last resource when changes in the liver have be- come too far advanced. The opera- tion performed before ascites has become a disturbing feature is some- times distinctly of value, particularly when the omentum is fixed to struc- tures extra to the peritoneum. The benefit of the Talma operation for Banti's disease is due to the lapa- rotomy and the resulting hyperemia rather than to the omentopexy. The latter helps, but the hyperemia from the laparotomy is the main factor, as determined in the course of 10 such cases. In operating the writer aims to induce hyperemia as much as pos- sible and to remove all traces of the ascites. If the kidneys are function- ing defectively, absorption of ascitic fluid left behind may prove fatal. He knows of two such deaths, and warns that pronounced kidney disease con- traindicates the operation, and that in all cases the general anesthesia should be as slight as possible. Bogojawlensky (Zentralbl. f. Chir., Feb. 27, 1909). Three cases in which the writer fol- lowed Ruotle's method of treating chronic ascites with cirrhosis of the liver by suturing the peripheral end of the saphenous vein, severed 8 cm. above its mouth, to the peritoneum just above Poupart's ligament. In the first case, a man of 38, the patient is well, with no return of ascites after the operation a year ago; in this case omentopexy, decapsulation of both kidneys, and continuous abdominal drainage had failed to cure. In the 2 other cases the ascites was the result of pericarditic pseudocirrhosis of the liver; here none of the operations done, including the Ruotle, gave re- lief. T. Soyesima (Deut. Zeit. f. Chir., April, 1909). Case in which the saphenous vein was severed and carried up into the peritoneal cavity through a sub- cutaneous tunnel. The condition was immeasurably improved, al- though at first there was much edema in legs and lower trunk. Toussaint (Gacete de la Acad, de Med., Mexico, Jan. -June, 1917). See also the article on Ascites in the second volume. Surgery of the Mesentery and Omentum. — Aside from surgical af- fections which involve the mesentery along with the intestines, the former sufifers from surgical afifections pecu- liar to itself, more especially solid tumors and cysts in the omentum and mesenteric folds. They do not, as a rule, cause acute or complete 62 ABDOMEN, SURGERY OF (MORRIS). ileus, but cause pressure symptoms, and if left alone tend to set up low- grade peritonitis and adhesions to neig-hboring viscera. These growths should be extirpated whenever operable. Cysts with dense adhesions and chylous cysts can only be managed by drainage. SURGICAL DISEASES OF THE INTESTINES.— Ileus.— Most of the conditions which require surgical in- tervention for the intestine, excepting traumatisms, are brought about by ileus or intestinal obstruction of some form. This is not the place to discuss the manifold agencies which produce obstruction, nor their recognition be- fore operaticm. Once acute obstruc- tion is evident, the surgeon is usually obliged to open the abdomen, his course afterward depending on the nature of the obstruction. In conditions like in- tussusception, volvulus, intestinal hernia, or obstruction adhesions, the obstructed loop is released, and steps described for the separate conditions are taken to prevent a recurrence ofi the trouble. If tlie mesentery is too long, or the intestine too mobile, a reef may be taken in the former, or the latter may be anchored to the abdominal wall or excised. If the intestine has become strangulated and is gangrenous, enterectomy is indicated with secondary anasto- mosis. If the obstruction is from foreign bodies, as with round-worms or gall-stones, for instance, the sub- stance should be worked back to an empty portion of intestine, and an enterectomy or colectomy for foreign boaies performed. If the loop of intes- tine shows serious changes as a result of obstruction, a temporan,^ artificial anus may be advisable. Excision is seldom required in such cases. In cases of acute ileus from any cause secondary peritonitis may develop and require treatment (see Peritoni- tis). While acute ileus may result from stricture or tumors, such condi- tions are much more apt to produce chronic stenosis, which ultimately u left alone will produce chronic ileus. Such cases naturally tend to coma to operation before ileus develops. Benign growths and cysts of the mesentery, and similar formations which do not compromise the integ- rity of the intestine may be removed without much interference with the latter. Tumors of the gut itself necessitate excision of the latter with secondary anastomosis, or establish- ment of artificial anus. Tubercu- lous strictures are treated by entero- clusion, or enterostomy for drainage, excision being, as a rule, contrain- dicated. The same is the alternative in inoperable carcinoma. Surgical relief of obstruction is the only final salvation for life, and should be instituted early before the patient has absorbed a lethal dose of poison. Tlie only excuse for the re- sponsil)le physician is the refusal of patient to accept his advice. An in- violable law should be to keep every- thing out of the stomach. Gastric lav- age should be practised to delay seri- ous symptoms until operation can be done, and the lost body fluids re- placed by proctoclysis and hypoder- moclysis both before and after opera- tion. Murphy's method with re- section of any area of damaged in- testinal wall is ideal in earlj- cases in the hands of a good technician, but it takes time and adds shock in late cases. The newer method of McKenna. of direct surgical drainage of the high intestinal area by a quick enterostomy high up in the jejunum, tides the patient over the crisis of acute toxemia. Six or eight weeks later, with the patient in good con- ABDOMEN, SURGERY OF (MORRIS). 63 dition the damaged and obstructed area can be resected. J. N. Jackson (Mo. State Med. Assoc. Jour., Sept, 1917). After abdominal operations there is usuallj' stasis for 24 hours, which acts as a protective measure. Enemas are given the day after operation. If there is no relief, lavage, laxatives, hypodermic injections of pitnitrin or eserine are given during the second night and third day. If these do not bring relief, it is concluded that the obstruction is complete. The patient vomits and is toxic. On the evening of the third day or the morning of the fourth he is taken to the oper- ating room and the incision opened. If there is general peritonitis an en- terostomy is made without explora- tion. If there is no peritonitis, ex- ploration is made and the cause, which is usually an adhesion, is re- moved; then, of course, enterostomy is not necessary. If operation is de- layed until late in the fourth day, toxic paresis may complicate the ex- isting conditions. C. H. Mayo (An- nals of Surg., Ixvi, 568, 1917). In performing enterostomy for postoperative obstruction, without an anesthetic, a few stitches are re- moved, the peritoneum opened, and the first distended coil of intestine which presents seized. Into it a purse-string suture of chromic catgut, in a circle at least ^ inch in diameter, is placed rather deeply. With the intestine held up by grasping the suture at 3 different points, a hole is burnt through the center of the circle with the Paquelin cautery, using the pointed tip. A rubber tube is then immediately passed through. The gut being elastic a tube twice the size of the opening may be used. The purse-string is now tied, invert- ing the margin. If conditions permit, a second purse-string is also intro- duced. It is a good plan, when pos- sible, to either stitch omentum about the tube or puncture the omentum and pass the tube through it. The tube is secured from slipping with strips of adhesive plaster. J. W. Long (Jour. Amer. Med. Assoc, Mar. 17, 1917). In intestinal obstruction following pelvic operations, 3 stages can be noted, those of onset, obstruction, and toxemia. Pain, distress, and vomiting, not relieved by gastric lavage or by enemata, are diagnostic signs, and if present, operation should be performed immediately. But often there is a delay of 24 hours before operation is done. Anspach (N. Y. Med. Jour., June 21, 1918). Analj'sis of 245 consecutive cases of intestinal obstruction. Of the 217 patients operated on, 76 died, a mor- tality of 36 per cent. The operations varied from such simple procedures as the untwisting of a volvulus or division of a constricting band to re- section of several feet of gangrenous bowel. The results seemed to de- pend far more on the condition of the patient at the time of the opera- tion, the long time elapsed since onset of sj-mptoms of obstruction, and the condition of the bowel, than on the nature of the surgical operation. Fin- ney (Surg., Gynec. and Obstet., May, 1921). Volvulus. — \'olvulus most often oc- curs in the pelvic colon, and conse- quently does not belong to this group of articles, but it may occur in the sigmoid or cecal region. In the latter case, after untwisting the volvulus and separating any peritoneal ad- hesions, a rectal tube should be passed and the poisonous contents of the volvulus massaged gently but rapidly toward the rectum, pro\ided that no gangrene of the volvulus be present. The prevention of recur- rence by approximation to the an- terior abdominal wall by Rosei^'s method is uncertain, and the author favors complete excision of the part oi the bowel engaged in volvulus, as this can readily enough be spared, and an end-to-end or lateral anastomosis of the remaining segment of bowel ful- 64 ABDOMEN, SURGERY OF (MORRIS). fills the indication. Volvulus of the cecal region occurs when there is a congenital form of defect giving a sort of mesocecum which may be quite long. Excision of the cecum and intestinal anastomosis are pref- erable to any attempt at preventing the recurrence of twisting of the cecum. Volvulus of the small intestine occurs most frequently when the coil of bowel is caught by an adhesion band, and peristaltic progress may loop the bowel in such a way as to cause torsion. In sigmoid volvulus the writer su- tures together, side to side, the lowest parts of the loop just untwisted. The opening must be 6 or 8 cm. long. The loop above is thus functionally excluded, and finally almost shrivels away. C. Pochhammer (Zentralbl. f. Chir., Feb. 14, 1920). The Grekow-Kummell invagination method for the radical cure of vol- vulus of the sigmoid flexure has cer- tain definite advantages over resec- tion. It is simple and brief and per- mits of both total removal of the flexure and absolute asepsis. The mobilized portion invaginated in the rectum sloughs off spontaneously and is expelled in a few days. Lange (Zentralbl. f. Chir., Oct. 30, 1920). Localized paralysis of the bowel occurring in typhoid fever may lead to this twisting of the bowel upon itself, and the twisted part can best be excised if the patient's condition allows it. Intussusception. — In a child with the patient under an anesthetic, an intussusception can sometiines be re- duced by the hands on the abdomen, but the last inch is very difficult of reduction, and we are likely to do damage by persistent efiforts. There is the same objection to water injec- tion, as we cannot know whether the last inch has been reduced or not. Furthermore it is very easy to rupture the bowel of a child. We may reduce an intussusception better through a very short incision, even though children bear the operation so badly. Perhaps it is best not to apply many of the resources for intussus- ception described in the older text- books, with the exception of operation by immediate laparotomy. There is no occasion in this article to describe the many varieties of intussusception, because the principles of treatment are practically the same in all. Re- duction of intussusception is so likely to be followed by recurrence that operation is an addition that is preferable in many cases. The part of the bowel engaged in intussuscep- tion is of no value, and consequently excision of the bowel with anasto- mosis is in order, unless the patient is in a desperate condition, in which case we may simply approximate any two loops of bowel above or below the intussusception and unite these in the common way with a Leinbert suture. Intussusception cannot progress beyond the point at which such anas- tomosis has been made. In emergency cases of intussuscep- tion, with the patient in extremis, the author likes the inethod of making a quick lateral anastomosis immediately above and below the area involved in the intussusception. If two traction sutures are used for approximating the loops of bowel to be anastomosed the work can be done very quickly and with little traumatism. The results of this procedure in emergency cases would seem almost to justify the simple resource as a regu- lar procedure. Intussusception cannot progress beyond the sutured area. The ABDOMEN, SURGERY OF (MORRIS). 65 invaginated part of the bowel in the as an opening at the umbilicus, but intussusception may slough or under- more commonly we have only the go subsequent atrophic changes with- patent part of the tube near the bowel out addino- a serious feature. with a cord-like remainder extending to the uml)ilicus. Foreign bodies may escape into this diverticulum, or ordinary- intestinal contents may result in exciting inflammation. Ad- hesions may produce angulation of the tube, interfering with circulation The diagnosis should be followed by immediate operation which should be performed with the minimum amount of handling of the intestine and traumatism. The best incision is one that splits the rectus at the junc- tion of its middle and inner third, and extends one-third above and two- and leading to infection. Sometimes thirds below the umbilicus. If pos- ^he diverticulum acts as a constrict- sible the tumor mass should be • ^^^^ -^ intestinal obstruction, in grasped with two fingers and brought , . , . , , ^ . ^ . 4. 4.U u 4^u ■ ■ ■ T} A ^*-^„ which case it takes part m acute in- out through the mcision. Reduction ^ is successful in between 80 and 90 flammatorv' process and may become per cent, of cases. Any other pro- gangrenous. Volvulus of the diver- cedure is so unsatisfactory that every ticulum mav OCCUr. effort should be made to complete Colonic Diverticula.— These mav reduction. Ir it fails, resection with . , r^ , ^ , ^ . u Ki f occur at anv point, and otten consist end-to-end anastomosis probablv oi- - ^ ' fers the best chance of recover>'; but ©f anatomic defects Opening into epi- the mortality is high, as the case is ploic appendages. Increased pressure usually a neglected one. Formation within the bowel at any time may lead to considerable enlargement of one or m.ore such diverticula, and later with obstruction and inflam- mation. As in the case of one of the writers, diverticulitis, particularly when situated about the sigmoid region, may result in of an artificial anus is attended with practically 100 per cent, mortality. Attempts to prevent recurrence by anchoring or shortening the mesen- tery are doubtful and prolong the operation. In closing the abdomen, tension sutures of silkworm gut should be inserted through the skin and aponeurosis, in addition to the perforation into adjoining structures. In laj-er sutures. Special efforts should be directed to combat shock. B. T. Tilton (N. Y. Med. Jour., Oct 7, 1916). Typhlitis. — Not readily distinguish- able from appendicitis, and is usually the writer's case there was penetration of the wall of the bladder and also of the ad- joining segment of the ileum. Resection of the whole area of the diverticula in- cluding practically the whole sigmoid, and also of the tissues of the bladder and treated by simple opening of the ji^^j^ ^y W. Wayne Babcock resulted in perfect recovery. Editors. Epiploic appendages when twisted upon their- long axes may become congested and even gangrenous in ven.^ fleshy patients, but the treat- ment is simply for abscess w^hich fol- lows. Diverticulitis of the sigmoid region abscess and drainage. Meckel's Diverticulum. — One of the remains of the vitelline duct is some- times attached to the convex border of the intestine, and varies consider- ably in range, as well as in character. In some cases it closely resembles the part of bowel from which it springs. Consequentlv all varieties call for is the most common, giving symp- their respective forms of treatment. toms quite similar to those of appen- Sometimes the entire tube remains dicitis, excepting for location of tender- 1—5 66 ABDOMEN, SURGERY OF (MORRIS). ness. The infiltrated tissues may re- spond to external applications of heat or cold, but frequently we must oper- ate for the abscess which remains. Report of several cases of diver- ticulitis. The writer has had suc- cess with temporary colotomy to rest the bowel, with subsequent resolu- tion of the inflammatory process, so that the colotomy wound could be closed and the lower part of the gut was able to function again. He has also inverted the projections, convert- ing them into polypi. Important to keep the bowels regular and to have the patient stop eating when symp- toms develop, if medical treatment is used. Turner (Lancet, Jan. 17, 1920). Wounds, Perforation from Within, etc. — In cases of solution of continu- ity in the intestine, whether from penetrating- wounds from without or perforation from ulcers within, the course of procedure is the same. Laparotomy is performed and the wound or perforation stitured, unless the wounds are multiple and so close together that suture would cause too great a reduction of caliber, in which case anastomosis may be necessary. TYPICAL OPERATIONS OF THE INTESTINE.— Enterorrhaphy. — This term is applied to suture of the intestine for wounds or ulcers which are not extensive enough to require excision and anastomosis. The chief amount of intervention is in connection with the external inci- sions and examination of the intestine to determine the extent of the injury, which may involve more than the bowel itself. Hemostasis and cleans- ing of the peritoneal cavity will necessarily be required in traumatism from without, as well as in perforat- ing ulcer from within. It will often be necessary to incise the mesentery in order to complete the examination. and these incisions must always be sutured in such a way as to leave no point uncovered by peritoneum. Perforation may, as a rule, be sutured without preliminary excision of tissue. The suture should run parallel with the long diameter save when the traumatism is near the pylorus. In this locality it should be applied in the transverse diameter. It is exceptional for an external traumatism to consist only of a single perforation of the intestine, for, as a rule, not only is the bowel itself penetrated doubly, but other portions of intestine and mesentery are in- volved in the knife or bullet wound. Hence single isolated trauma occurs most naturally from the internal perforations. Multiple perforations of the bow^el and mesentery are adaptable for suture, no matter how numerous, if they are not too close together; but, when a portion of bowel is, so to speak, riddled by bullet or other wotmds, it should be excised, unless the author's resource in one case quoted above introduces a principle in addition. For suturing perforations a few points of interrupted Lembert silk or linen suture are usually sufficient. In multiple perforation or when there is suspicion of such, it is advisable to suture as soon as the wound is located, and before proceeding with further examination. The rule for determining the pos- sible limit of suture in contrast to excision is this : if the suture of one or more openings does not diminish the caliber of the intestine by more than a third, suture is indicated in place of excision. In perforation from typhoid ulcer ABDOMEN, SURGERY OF (MORRIS). 67 multiple traumatism is unusual, and the lesion in most cases is seated not far from the ileocecal valve. Owing- to the general state of the patient the operation must be rapidly done, as a rule. An appendicitis incision usually suffices. The perforation is closed at once by a few interrupted sutures, or a purse-string suture. Cases of typhoid perforation do occur in which, either from the size, number or complica- tions of the lesion, enterostomy or enterectomy is required, but the con- dition of the patient sometimes makes it desirable to quickly fasten the bowel opening near to the external opening, and to do a secondary exci- sion operation after recover}^ from the typhoid. The friable character of tissues distended with serous in- filtrates also makes this expediency work necessarv' when the friable tis- sues refuse to bend freely to sutures. Even after simple suture it may not be advisable to close the abdominal wound, in contradistinction to the course pursued in suture of external wounds. The presence of peritonitis with adhesions may make it advan- tageous to leave the lower angle of the wound open for the purpose of a little drainage. Review of the literature of intes- tinal perforation in typhoid fever showed that those operated upon in which perforation was found con- sisted of 269 cases (from 1903 to 1909): 156 of this number resulted fatally, giving a mortality of 57.99 per cent., while Harte and Ashhurst (all cases from 1884 to 1903), in a similar study, found 311 cases, with a mor- tality of 73.31 per cent. Charles Bag- ley, Jr. (Surg., Gynec. and Obstet., Aug., 1911). In a search through the literature since 1903, the writer found 133 re- ported cases of typhoid fever in which perforation occurred and was closed by suture. Of this number 68.5 per cent, died and 31.5 per cent, recov- ered. G. D. Head (Jour. Minn. State Med. Assoc, Aug. 1, 1911). Enterectomy. — Excision of portions of intestine is performed for a great varietv of conditions, such as trau- matism, malignant tumors, actual or impending gangrene, etc. It is indi- cated, therefore, as an operation oi choice or necessity in many of the conditions which constitute or give rise to ileus. The part to be removed may vary in length from two or three inches to a number of feet. In enter- ectomy, as in similar operations, the actual operation requires much less time and a much simpler technique than the secondar\^ stage of restoring the continuity of the intestine. There is in fact but one technique for the former, while the latter is not only practicable by quite different opera- tions, but each operation may be per- formed bv a number of different methods. For the performance of the enter- ectomy proper, it is necessary to excise a portion of intestine with a certain amount of mesenter>'. After the external incisions and exploration of the abdomen the portion of intes- tine to be excised is, if necessarv^ freed from adhesions. This coil of intestine should be milked into the portions of the gut continuous, for which purpose the fingers of assist- ants must be used. After one-half of the coil is thus emptied in one direc- tion the fingers should compress the gut to prevent re-entrance of intes- tinal contents ; the other extremity is then similarly treated. Instead of the fing-ers of assistants, clamps may be applied, one at either end and 68 ABDOMEN, SURGERY OF (MORRIS), some inches beyond the segment of gut to be excised. Loops of gauze may also be used, but in such a case the mesentery must be penetrated, and it is best to use the fingers of assistants as far as possible. Before excising, the mesentery must be ligated off close to the intes- tine,— about one inch distance. An approximate rule is to place a catgut ligature for every inch of mesentery. Another is to ligate less rather than more mesentery than is apparently called for. This is done on the prin- ciple of overcorrection, because if too much mesentery is sacrificed the edges of the anastomosis to be per- formed may suffer gangrene from interference with blood-supply. When all preliminaries have been completed the gut with its mesenteric stump is removed by means of the scissors. Case of resection of 300 cm. (10 feet) of the small intestine and the cecum, with 20 cm. of ascending colon, owing to extensive ileocecal tuberculosis. The patient left the hospital at the end of the fourth week, having about 3 stools a day, but 2 months after operation he returned with a severe cold and died shortly afterward of acute tuberculosis. Post- mortem examination showed the ab- domen in excellent condition. The remaining small intestine up to the duodenojejunal juncture was only 5 feet, 7 inches, in length. Canaday (Annals of Surg., Ixix, 425, 1919). Report of experiments supporting Payr's disinfecting method of mu- cous membrane of the intestine by painting with a 5 per cent, solution of iodine. In 67 per cent, of cases the iodine produced sterility, and in 33 per cent, the number of bacteria was decreased. The procedure is es- pecially of value in the lower parts of the colon. L. Frankenthal (Beitr. z. klin. Chir., cxx, 614, 1920). Report of 282 consecutive cases of acute intestinal obstruction operated on, comprising 170 cases of obstruc- tion due to external hernia, 42 cases of carcinoma, and 70 other cases ot obstruction. Saline infusion and morphine were used. The mortality was 9.3 per cent, in the cases not requiring resection and 47.8 per cent, in those requiring re- section. Experience in determining whether the intestine is viable or not is important. When the walls are of an abnormal color and, in addition, feel limp and offer no sensation of firmness to the fingers, recovery is unlikely. E. R. Flint (Brit. Med. Jour., May 21, 1921). Enteroanastomoses. — These meth- ods of restoring continuity of the intestine after enterectomy comprise three distinct types. The first and most natural is end-to-end anasto- mosis or suture, which in most cases is the operation to choose. The second type is known as. the side-to-side laterolateral or simply lateral. It differs in scope from the preceding chiefly because it may be used between the small and large intestines, and small intestines and stomach. In acute intestinal obstructions from adhesions, unless the adhesions can be easily broken up, it is better to leave them alone. The loops above and below the obstruction should be joined by side-to-side anastomosis. The writer describes 7 cases in which he did this, with recovery and good results in 6 instances. If it is con- sidered best to resect the excluded segment, this can be done later after the general condition has improved. The intestine may be twisted when bound down by bands, and the circu- lation be so impaired that the slightest traction causes rupture. Ingebrigtsen (Norsk Mag. f. Laegevid., Feb., 1921). The third type is known as end-to- side or terminolateral, or simply as ABDOMEX, SURGERY OF (MORRIS). 69 the implantation method. It is re- contents to escape in case of good stricted in practice to implantation of digestion, and defect of pyloric diges- a cut end of small intestine into the tion would be the result. In addition, stomach or colon. The first-named cases have been reported in which has already been considered in part jejunal ulcer has followed the form- under pylorectomy. The latter is ing of an opening at a point where specifically known as ileocolostomy, acid contents could injure the tissues, or ileosigmoidostomy. The choice of procedure in gastro- Gastroenterostomy. — This operation enterostomy at the present time is consists of a lateral anastomosis certainly the so-called posterior no- between the stomach and some loop operation, but the author has portion of the small intestine, either referred to older operations which the duodenum or jejunum. Accord- are necessary at times. Even with ing as the intestine is united to the ulcer of the stomach in the cardiac anterior or posterior stomach wall end of the stomach, the posterior no- the operation is known as anterior or loop operation should be made with posterior gastroenterostomy. the pylorus, if possible, to avoid the The operation is indicated in effects of gastric acidity at some certain cases of gastric or duodenal distant point from the pylorus. The ulcer, either as a primary resource or posterior no-loop operation is per- one secondar\' to pylorectomy or gas- formed by making an opening trorrhaphy. Generally speaking the through the transverse mesocolon in operation is one of necessity when the usual way, avoiding the middle milder measures have failed or are colic vessels. The posterior surface likely to fail. Minor indications for of the stomach being exposed, a gastroenterostomy are found in con- portion near the pylorus part is traction of the pylorus from swallow- chosen and drawn through the open- ing corrosive poison, in some cases of ing. The jejunal flexure close to the congenital stenosis of the pylorus, duodenum is found beneath the left and finally in certain cases of cancer of the mesocolon, and the proximal in this locality, as a palliative when loop is employed for completing the pylorectomy cannot be performed. gastroenterostomy, in such a way The operation is contraindicated in that when the parts are released from so-called medical diseases of the the fingers or clamps the intestine stomach, however severe these may will hang in a direction which is be. almost vertical, but with a slight The ideal operation is one in which inclination toward the left or right, the opening is made as nearly as we in a normal line of the long axis of can to the pylorus and the proximal the individual jejunum. This is the loop of jejunum, thus utilizing the part essential part of the posterior no-loop of the stomach which is commonly the operation. lowest during the process of diges- Of '^'^^ cases in which the writer tion. This will allow free regurgita- \f^ r^^on^A to gastroenterostomy, , 11 1- • • r • • I'O were male and 103 female. The tion to the alkalme mtestmal juices. ^^^^^^^ ^^^ ^^ ^.^^^^ ^^^ operation Anastomosis with the cardiac part ^as done was 44.3 years for males of the stomach would allow acid and 41.5 years for females. In those 70 ABDOMEN, SURGERY OF (MORRIS). cases seen shortly after operation in which one would not expect total restoration of gastric function, 20.9 per cent, were free from complaint; 49.8 per cent, were clinically com- fortable, and in 87.89 per cent, subjec- tive benefit had resulted. F. Smithies (Surg., Gynec. and Obstet., xxvi, 275, 1918). The writer strongly advises loca- tion of the anastomotic orifice at the dependent point of the pyloric vesti- bule, as near as possible to the greater curvature of the stomach. Posterior gastroenterostomy as ordinarily per- formed does not always permit of recognition by the operator of the exact point of the stomach which he is bringing up through the narrow slit in the mesocolon. To obviate this, he recommends Lardennois and Okinczyc's procedure of stripping the omentum from the colon, which al- lows the operator to expose the entire posterior surface of the stomach. The anastomosis having been effected, the margins of the opening in the meso- colon are simply sutured through the posterior cavity, and the great omen- tum is brought down over the trans- verse colon. P. Duval (Presse med.. Mar. 13, 1919). Regulation of the size of the gastro- enterostomy opening recommended. Where there is gastric atony, the contents will pour out too quickly unless the opening is small; j'ct it should be at the lowest point. With hypertonicity and a need for resting the stomach, the opening should be large and in the antrum, near the lesser curvature. If later required, the pylorus can then be closed. Metivet (Presse med., Jan. 28, 1920). The cause of jejunal ulcer after gastroenterostomy is the pouring of acid gastric juice directly into the jejunum, which is physiologically fit- ted for only alkaline contents. Ac- cepted treatment of jejunal ulcer after gastroenterostomy is to disconnect the gastroenterostomy and perform a pyloroplasty. If a pyloroplasty had been done in the first instance, the jejunal ulcer would have been avoided. The writer had a case of jejunal ul- cer that occurred on the mesenteric border of the jejunum opposite the gastroenterostomy. J. Shelton Hors- ley (Trans. So. Surg. Soc; Jour. Amer. Med. Assoc, Jan. 15, 1921). Stress laid on the superiority of trans- and supra-mesocolic gastro- enterostomy over ordinary posterior gastroenterostomy. W'hen the for- mer is performed in simple cases it is not necessary to bring the trans- verse colon to the surface of the body. In difficult cases this allows the surgeon to operate outside the abdomen, and to place the opening in a good position. If the operative in- dication is clear, if exploration of all the posterior surface of the stomach is not necessary, and if the gastro- enterostomy is only the first stage of a gastrectomy, the gastrocolic liga- ment is depressed with the finger and the posterior wall of the stomach is exposed. If a very wide exploration of all the posterior wall of the stom- ach is necessary the intercolo-omental exposure of Duval is done. If pyloric exclusion by section is indicated and there is no suitable area on the pos- terior wall of the stomach to make the anastomosis the greater curvature is stripped of its vessels. R. Toupet (Presse med., xxix, 253, 1921). When postoperative jejunal ulcer occurs, the basis for it is usually laid during the first few weeks or months following gastroenterostomy, owing to neglect of dietetic precau- tions. Light and more frequent meals than normally are indicated. In other respects the diet should be regulated as in cases of gastric hyper- secretion. The marked acid-combin- ing capacity of casein and the inhibi- tory effect of fats on gastric secre- tion are emphasized. Cottage cheese, thoroughly mixed with milk or cream or softened and loosened up by stir- ring in beaten whites of eggs, with sugar, should be used plentifully, be- ginning a few days after the opera- tion. Of the fats, that of boiled beef, fresh and melted butter or, still bet- ter, vegetable oils (from 1 to 2 table- ABDOMEN, SURGERY OF (MORRIS). 71 spoonfuls after eating), are indicated. The antacid effect of the oils is more marked if taken separately than if mixed with the food. For the first 3 weeks after the operation, the writer recommends a diet of boiled milk, fresh cottage cheese, 2 or 3 soft boiled eggs, fine wheat bread, butter, gruels and plain rice dishes. Later, mild cheese, mashed potatoes, vegetables passed through a sieve, and cooked fruits may be added. This diet should be adhered to for from 6 to 8 weeks, all meat or raw vegetables being ex- cluded. Favorite dishes and appetiz- ing odors should be scrupulously avoided, to obviate "psychic" gastric secretion. Von Noorden (Therap. Halb-Monatsh., Apr. 1, 1921). If the edges of the cut mesocolon are fastened to the stomach wall before completing- this gastroenteros- tomy, it will obliterate the opening- in the mesocolon, and this is desirable for avoiding subsequent hernia, if the patient's condition allows us to follow ideal technique. When adhe- sions or extensive scarring or other mechanical reasons make the pos- terior no-loop operation of gastrojejun- ostomy difificult, we may use gastro- duodenostomy, instead. The anterior wall of the pylorus is joined with the ■descending part of the duodenum, but where we suture the mesocolon to the stomach it avoids the danger of sub- sequent hernia. It is practicable to insert a pre- viously swallowed Rehfuss gastro- duodenal tube well into the jejunum and to cominence at once, on the operating table, the feeding of pep- tonized milk, dextrose and alcohol mixtures. Immediate jejunal feeding after gastroenterostomy is not only to be recommended in the operations performed for stenosis, but should be tried in all types of cases. Andresen (Annals of Surg., May, 1918). Anterior Gastroenterostomy. — This, the original procedure, has been replaced in most cases by the posterior operation, but is still per- formed when the posterior wall is unaccessible by reason of adhesions or organic disease. A fairly good rule is for the surgeon to do which- ever operation he can do most easily in any given case, but the anterior operation gives more postoperative complications. The operation is as follows : — After the stomach has been fully exposed, its anterior wall is so grasped that the fold which is to be the seat of the anastomosis runs obliquely across from right to left, and from below upward. The intes- tine is similarly grasped about eighteen inches below the duodeno- jejunal junction and the two struc- tures placed side by side. The anastomosis is then carried out as in all similar procedures, one- half the outer plane of sutures being inserted before the incision is made. Details of technique will be con- sidered under the posterior operation. Posterior Gastroenterostomy. — The external incision is that used for other operations on the lower portion of the stomach and the pylorus, passing through the right rectus by blunt dissection, the posterior sheath and peritoneum being divided together. The incision is largely an explorator)'- one, for despite the evi- dence of a pyloric ulcer, for example, the entire stomach and duodenum with the neighboring viscera must be examined for complications and pos- sible contraindications. The jejunum must also be examined with especial reference to its relations with other organs. The natural direction should be learned, for this may be to the right, left, or directly downward, and 72 ABDOMEN, SURGERY OF (MORRIS), in bringing" the intestine in contact with the posterior wall the original direction must be conserved. In order to gain access to the posterior wall it is necessary to go through the transverse mesocolon, the incision being ample enough to enable the posterior wall to be drawn outward ; but the incision in the meso- colon, to avoid opening large blood- vessels, should be first made small and then enlarged by stretching with the fingers. Generally speaking the portion of this wall to be selected for anasto- mosis is at tile lowest point of the organ, which is considerably nearer to the pylorus than to the cardia and fundus. The author likes to cut through the ligament of Treitz when approaching the posterior stomach wall. This brings one to a convenient part of the jejunum for the no-loop operation. He prefers traction sutures rather than instruments for approxi- mating stomach and ileum during op- erative procedure. The portion to be incised for the anastomosis is pinched up in a direction corresponding to the natural direction of the jejunum itself. The latter is also grasped an inch or two below the duodenojejunal junction. As in all such anastomoses, a portion of the outer plane of sutures is intro- duced before the incisions are made. This is a continuous seromuscular suture, intended to fix the two structures together and furnish a guide to the incisions. The latter, some three inches in length, are not simple linear incisions, but a small spindle-shaped portion of tissue is excised. The two openings thus made are now sutured together by through-and-through stitches of the penetrating type, the two posterior margins being first united, and then the anterior margins, the inner layer of sutures being thus completed. The fingers or clamps are removed, and the outer plane of serous sutures completed. Tn performing the posterior opera- tion the writer advises that the oper- ator locate the peritoneal suspensory ligament or band which extends from the transverse mesocolon to the upper part of the jejunum. Immediately above this band, in the mesocolon, is an area in which there are no impor- tant blood-vessels. The suspensory band having been stripped away, and a transverse incision made in the above-mentioned area of the meso- colon, the posterior aspect of the stomach may be drawn through this opening and the denuded jejunum at- tached to it, the attachment thus be- ing without strain or loop and follow- ing the normal direction of the jejunum. Mayo (Annals of Surg., Jan., 1908). New method of gastroenterostomy accompanied by less traumatism to tissues than where clamps are used, sure to be free from postoperative hemorrhage, and more readily per- formed. .A celluloid suture is inserted through the stomach and intestine at each end of the sites chosen for the new communication. By keeping traction on these, the jejunum and stomach are kept in close approxima- tion. The usual posterior stitch is next introduced. The peritoneal cav- ity is then walled off and incisions made in both viscera close to the line of suture exposing the blood-vessels. These, usually 5 or 6 in number, are doubly secured with hemostats and the mucosa opened between them. Taking first the posterior wall, each pair of vessels, one gastric and one intestinal, is Hgated with a single strand of chromic catgut, after draw- ing the edges together by means of the two forceps in closest proximity. These ligatures not only prevent any hemorrhage, but hold the edges of ABDOMEN, SURGERY OF (MORRIS). 7Z the mucosa in firm apposition. The too-hne suture material which cuts anterior edges are drawn together by ^y^ when the patient vomits. In beginning at the end farthest from ^leedin^ ulcer of the stomach it is the surgeon. The 2 forceps which '^ j-£c i.u 4. ,. . , ^, ^,^ 1 „,,, ^^ sometimes extremely dimcult to he opposite each other are held to- J gether by an assistant. The right end recognize all of the bleedmg surface of the ligature is passed around the while the tissues are held in tension, forceps on the intestine from right to Relaxation of tissues and pressure on left, the left end is passed around the ^^^ viscera with the fingers or with forceps on the intestine from lett to ^ u_ r ui j- 1 • i . , , ,, , K^ srauze may start a free bleedmg which right so that the ends emerge be- ^°- : ^ tween the forceps, beneath the loop localizes the ulcerated area, Post- of the ligature. The forceps are now operative ileus may develop, which brought parallel to the long axis of .^^^ \y^ ^^^ ^-q obstruction from adhe- the wound, and rolled toward each ^.^^^^ ^^ internal strangulation, or to other, inverting the mucous edges or . _x- 1 1 • , , ' , ^* , ..^ -^^ ^r angulation of bowel, particularly in the wound. Each succeeding pair ot & _ ' ^ 1 1 • vessels is dealt with in the same way. the anterior operation, if the loop is The rest of the procedure is much as not supported by side sutures in the in the usual operation. Of the last omentum. 40 patients, 38 recovered and 2 died. ^^^^^ '^^^^ vomiting, which is these 2 having inoperable carcinoma . ^ , . , and succumbing to exhaustion and symptomatic of this obstruction, we pneumonia. F. T. Stewart (Annals may have a non-obstructive type of Surg., Ixvi, 334, 1917). which supervenes at a late period Rour's Operation. — The Y-opera- (one or two months following opera- tion of Roux differs notably from the tion). The nature of the vomiting is typical procedures just enumerated, not always clear, but, since operators being a combination of the anasto- have sought to preserve the natural moses, both being examples of im- direction of the jejunum, cases of plantation of terminolateral anasto- obstruction and vomiting have been moses. The jejunum having been much less frequent, divided across, the peripheral seg- A complication of considerable grav- ment is implanted i-nto the posterior ity is peptic ulcer of the jejunum, at- surface of the stomach, while the tributed once to the action of digestive proximal segment is implanted into enzymes, but now regarded as having the jejunum. a common origin with ordinarv^ gastric It is no longer held desirable to use and duodenal ulcer, viz., hyperacidity mechanical devices in most gastro- (hyperchlorhydria) and toxic injury enterostomies, although such aids of terminal arteries. To lessen the fre- were of great importance at one time quencv of this complication it is ad- in giving us confidence to advance visable that every patient to be to a simpler technique. operated upon be first treated for Gastroenterostomy is liable to be hvperchlorhydria. Peptic ulcers of the succeeded by certain typical compli- jejunum run a similar course to that cations. Among these are hemor- of ulcers higher up, terminating at rhages, sometimes inexplicable, but times in perforation. now generally believed to be due fre- Condition of the patient one year quently to overlooked ulcers, or to or more after gastroenterostomy in imperfect suturing, or to the use o£ 175 cases, 150 benign, 25 malignant:— 74 ABDOMEN, SURGERY OF (MORRIS). Benign Cases (ISO). — The immediate mortality (death within thirty-five days) was 10 per cent. Eighteen died within the first year (12 per cent.); 22 died of their gastric disorder within five years (14.6 per cent.). Six patients are alive, but have been oper- ated upon within one year. Of the 126 patients who survived the operation, and have been under observation for one year or more, 81 (or nearly two-thirds) were reported as entirely recovered, or well; 8 as much better, and 31 (nearly 1 in 4) as little or no better. Of the 150 patients 89, or 60 per cent., were much better or entirely well; fully 30 per cent, died or were little or no better at the time of report. Twenty-five cancer cases are re- ported, 20 being in men. Ten patients died within one month of the opera- tion, an immediate mortality of 40 per cent. One is still living, two years after operation, another six months, and another four months. Ten pa- tients lived more than four months after operation. Six of these were temporarily much improved, and gains of weight ranging from eighteen to forty-seven pounds are recorded. Two patients received no benefit at all from the operation. Bettmann and White (Med. Record, Oct. 9, 1909). In gastroenterostomy the new formed anastomosis is the site of a healing ulcerated surface for a period of 14 days, and for the first 5 or 7 days, the process is largely destruc- tive. For the first 2 weeks, the diet should be as light as is compatible with maintenance of strength. Flint (Annals of Surg., Feb., 1917). The new train of symptoms some- times following gastroenterostomy is usually due to peptic ulcers in the stomach or bowel in the vicinity of the new stoma, or adhesions. All of these various complications or disturbances usually yield to a liquid diet, large doses of bismuth, and gastric lavage, but when these fail, duodenal or jejunal alimentation is of great benefit. Of 10 such cases 8 were so much improved that no further treatment was necessary. Max Einhorn (Med. Rec, June 16, 1917). Case of spasmodic occlusion of the anastomotic mouth after gastroen- terostomy in which complete success was obtained by administering bella- doima. The author is satisfied that his patient like Zwcig's was vago- tonic, with gastric hypertonia. L. Urrutia (Arch, des mal de I'Appar. digestif, Ix, 84, 1917). Fatal postoperative diarrhea some- times occurs. Its nature is obscure and seems to depend upon derang"e- ment of bow^el function due to shock to the sympathetic ganglia. End-to-end Anastomosis after En- terectomy. — This may be effected by suture, or JVlurphy's button. The suture methods in use comprise the simple direct suture, the combination of suture and invagination, the Connell method, etc. Simple Suture. — The mesentery is first united by transiixing both the cut edge of the gut just beside the mesentery, and then the latter close to its insertion. The same through- and-through suture is then passed in the reverse order through the opposite mesentery and gut. A duplicate suture is now passed through the other side, or the same suture may have its other end threaded in a needle and be used for this purpose. When this suture is tightened the gap in the mesentery is closed with approximation of the cut ends. The remaining step is suture of the latter, and this mav be done bv carrving the original two-tailed mesenteric suture from its knot around the circum- ference of the gut on either side until most of the circumference has been sutured. The opening which remains is closed with an outside Lembert suture. The rent in the mesentery is closed with a few points of catgut. ABDOMEN, SURGERY OF (MORRIS). 75 Intestinal anastomosis by invagina- tion, cuff and suture, is probably the simplest, quickest, safest, easiest method and the freest from unpleas- ant complications. The proximal end should extend from 1 to 1^1! inches into the distal end in end-to-end anastomosis, though less in lateral anastomosis. The invaginated ends and portions of gut eventually atrophy without stenosis. Fine round needles, silk or linen thread, and interrupted rather than continuous sutures should be used. B. M. Ricketts (Trans. West. Surg, and Gynec. Assoc, 1919). Maiinsell's Method. — The divided surfaces of intestine are placed in rough apposition by four traction sutures at equidistant points, the first at the mesenteric insertion. The next step is to introduce a pair of forceps through the intestinal wall from without inward, and to this end a slit is made in the long diameter of the bowel, one (either side) segment opposite the mesenteric insertion and about one and one-half inches from the cut edge. With this forceps the loose ends of the traction su- tures, previously twisted together, are tightened with production of an in- vagination of the distal into the proximate segment, the two serous icoats being in contact. In this posi- tion the two edges are united with a chromicized-gut suture applied through-and-through, the traction su- tures are removed, and the invagi- nated segment replaced. An external durable Lembert suture is now ap- plied. Connell Method. — As in the preced- ing operation, four traction sutures are applied, and the two cut edges of intestine are sutured, one-fourth at a time. The traction sutures which limit each quadrant are tightened in turn, and the intervening intestine joined by applying a right-angled through-and-through suture. As soon as a portion of the gut is reunited one of the tractors becomes unneces- sarv and is removed. At the close of the suturing the two free ends are threaded within the lumen of the intestine upon a ligature carrier, brought outside and tied, and the knot is then worked back on the inside of the gut. New method of aseptic enterec- tomy and enteroanastomosis is de- scribed, which is based on crushing with clamps of the visceral layers of the parts operated on. In end to end anastomosis, Kocher forceps are placed at the margins of the pre- viously crushed sections of bowel, and the piece of bowel to be taken out removed by passing the scalpel along the closed forceps. The 2 for- ceps are then placed side by side, and 2 continuous seroserous sutures carried successfully through the ad- joining bowel tissues along one side of the forceps, next round their tips, and finally back again along the other side. The forceps are then removed — the bowel ends having already been united all around except at one point, the point of entrance of the forceps — and a grooved director is passed in and moved from side to side, thus de- taching the previously adherent mar- gins of the serous coats, unfolding the mucous and muscular coats, and restoring communication between the two bowel ends. The suture ends hanging out are now tied, thus clos- ing the opening. In laterolateral anastomosis, as in gastroenteros- tomy, the 2 linear portions of visceral wall to be joined are first crushed; 2 continuous sutures are then passed completely round these portions ex- cept at one point, through which scissors are introduced to cut through the serous coats before the sutures are tied. The perfect results ob- 76 ABDOMEN, SURGERY OF (MORRIS). tained were confirmed bj' post-mor- tem examinations. Gudin (Paris Med., Dec. 16, 1916). Axial or end-to-end anastomosis of the colon has not hitherto been pop- ular because of its high mortality. The author points out that the real reason why axial union often failed is that the arteries supplying the colon pass round in a circular direc- tion with very little anastomosis. Leakage after axial union is gener- ally on the side opposite to the mes- entery. All that is necessary to se- cure a good result in axial anasto- mosis is to cut the bowel across at an angle of 45 degrees from the mesentery outward, i.e., with more insertion. The tails are then carried down on either aspect of the intes- tinal segment to the point opposite the mesenteric insertion, the suture of chromicized gut being applied overhand. The two tails of the suture having been tightened upon the halves of the button, these are then joined and locked. The rent in the mesenters- is now repaired and an outside durable Lembert suture ap- plied over the inside suture. Great care is taken to cover the bowel inci- sion with i>eritoneum at the mesen- teric attachment. Closed. Oblongr Murphy button. Open. bowel removed on the free than the attached side, thus insuring a good blood-supply to the whole of the sutured edges. The writer has used this method for j-ears. with almost uniformly perfect results. With the resected portion of bowel a wedge of mesentery is removed. The bowels are moved on the second day by a small gruel enema, assisted, if neces- sary by pituitary extract. P. Lock- hart-Mummery (Surg., Gynec. and Obstet., Feb., 1917). Murphy Button. — Purse-string su- tures are applied at either divided segment and tightened upon the halves of the button. The suture for each side is a two-tailed one, and first transfixes the mesentery at its Lateral Anastomosis. — In this oper- ation there is no restoration of the continuity originally present, but a purely artificial opening is created between the two segments of intes- tine. Such an operation may be termed an internal enterostomy, which agrees with an external colos- tomy to this extent: that in each case a fistulous commtinication is set up. In this connection we need only describe the operations of entero- enteric anastomosis and ileocolos- tomy, for the gastroenteroanasto- moses are considered elsewhere. This anastomosis may be effected in several ways — preferably by su- ABDOMEN, SURGERY OF (MORRIS). 77 ture, clamps, elastic ligature, or Murphy's button may be desirable in special cases. Suture. — The loop of intestine is emptied and prevented from refilling by finger pressure, clamps, or gauze loops. Excision having been per- formed, the two cut ends are closed by the insertion of inverting Lembert sutures, the slack of the mesentery being included in the inversion. A double cul-de-sac thus results, the two parts of which are to be joined in the resulting lateral anastomosis. The two ends are apposed for a space of four inches or more, and a single line of Lembert sutures applied at their junction. The segments being now in their permanent position, they are incised close to the suture line with scissors. As a rule, the length of the incisions should be three inches. A continuous suture of chromicized gut is carried along both sides of the new opening, thus constituting the inside suture plane. The out- side plane is completed by a second durable Lembert suture. Of mechani- cal aids. Murphy's oblong button is the best for general use, the tech- nique being akin to that of the round button for end-to-end anastomosis. Enteroexclusion. — The temporary operation is not a procedure compara- tive to enterectomy. It is without some of the dangers of the radical operation, and may be performed rapidly. The operation consists in division of the intestine and lateral enteroanastomosis, or, in the case of the colon, enteroimplantation. A dis- eased portion of the intestine which would otherwise demand extirpation is then excluded from the intestine. If the distal end is closed the opera- tion is known as partial or unilateral exclusion; but, if it is also made the subject of an anastomosis, the intervention is known as double or complete occlusion. The chief indi- cations are tuberculosis, fistulae (espe- cially multiple ones), and malignant disease. Unilateral Exclusion. — No attempt is made to close the excluded loop at its lower extremity, which is just above the anastomosis, as there is no danger of stagnation of feces in this locality. Technically the operation is well adapted for the use of ]\Iurphy buttons. No details need be given, as these are identical with the details of anastomoses after excisions. Its chief use is in emergency' cases. Bilateral Exclusion. — Both ends of the excluded loop are closed, and either two anastomoses are made or one end only is anastomosed while the other is left in the external wound. When the operation has been done for actual intestinal fistulse, both ends of the loop may be closed, as the loop will then be drained suffi- ciently through the fistulous open- ings. If exclusion is done for carcinoma it is better to leave one end of the loop in the external wound, for, when the operation has been done for any incurable condition, exclusion must be followed sooner or later by excision. The writer warns against opera- tions on the intestinal tract in which no outlet is provided for the intes- tinal mucous secretion. This over- sight sometimes leads to fatal results. When stimulated into greater activity by irrigation or infection, the amount of secretion may be enormous, as in colitis, and even result fatally. G. G. Turner (Brit. Med. Jour., iv, 227, 1916). Where a patient with toxemia only from the small bowel becomes a sur- 78 ABDOMEN, SURGERY OF (MORRIS). gical case, the writer considers the Lane short circuit ileocolostomy the operation of choice, but if, as is usually the case, the obstructed ileum is accompanied by a dilated and atonic cecum, the Mayo right-sided colectomy is the proper operation. The Mayo technique is free from the criticism of the Lane technique, in that the intestines are not handled after the colon has been opened, greatly lessening the possibility of in- fection, while there is no blind pocket left to become impacted. R. Smith (Surg., Gynec. and Obstet., Nov., 1916). Actual colectomy must be aban- doned as impracticable because of late unpleasant complications. Even after simple ileosigmoidostomy, pro- nounced anastalsis supervenes, ag- gravating the toxemia. In what the writer terms physiological colectomy, after the ileosigmoidostomy with side to side anastomosis has been estab- lished, the sigmoid is divided in its upper arch as near as practicable to the lower end of the distal sigmoid. The open end of the distal segment is then fixed in the lower angle of the wound and the open end of the proxi- mal colon in the upper angle. Fin- ally, a catheter — afferent — is inserted into the open terminal ileum, the tip being carried into the cecum, and a large tube — efferent — into the open end of the colon. Thus isolated, the colon is irrigated to unload its toxic fecal content and then left to atrophy from disuse. Where a secondary actual extirpation becomes necessary, the difficulties are diminished owing to the atrophy of the colon. The primary mortality from physiological colectomy should be practically nil, though as yet the percentage of ulti- mate recoveries have not been en- tirely satisfactory. C. A. L. Reed. (Trans. Amer. Med. Assoc; N. Y. Med. Jour., June 30, 1917). Enterostomy, Jejunostomy, Ileos- tomy.— The establishment of an arti- ficial opening- in the small intestine is not necessarily for the purpose of establishing an anus contra naturam, but may be done simply for relief of distention or, like gastrostomy, for tiie introduction of nutriment. The only condition justifying this form of intervention is an absolutely irre- mediable stricture of the pylorus with resulting star\'ation. The operation may be done like a gastrostomy, using a tube or catheter. It is preferable, however, to sacrifice the integrity of the intestine by divi- sion and anastomosis, leaving a cut end in the external wound. The point selected is in the jejunum, about eight inclies below the duodeno- jejunal angle. The intestine is divided at this point and the central end implanted six or eight inches farther along the gut. The peripheral end is not treated like the stomach cone in gastrostomy, i.e., it is passed out of the external incision, beneath the skin, and out at a special opening (see Gastrostomy^. The original wound is closed plane by plane while the fistular w^ound is sutured to the divided intestine. Ileostomv is sometimes performed for establishing an artificial anus, necessarily in cases where ileocolos- tomy or simple colostomy is insuffi- cient for drainage. The lowest pos- sible part of the ileum is selected, the incision being made one and one-half inches above Poupart's ligament. In this operation it is not necessary to divide the intestine, and the technique does not differ from that of ordinary colostomy. Jejunostomy advised for the relief of obstruction following operation, in cases of long standing acute obstruc- tion from some unknown cause, and for nutritive purposes in cases of widespread cancer of the stomach ob- structing the cardia and leaving little ABDOMEN, SURGERY OF (MORRIS). 79 room for gastrostomy, cases of ex- tensive laceration of a cancer of the stomach made accidentally during ex- ploration, and extreme cases of nerv- ous vomiting of girls from 18 to 25 years of age. The operation for pur- poses of nutrition is performed through a midline or left lateral in- cision; for the relief of obstruction it is best to re-open the former incision unless it is infected. In obstruction cases the operation should be per- formed as soon as the evening of the third day or on the fourth day. If there is no general peritonitis and the obstructive condition is recognized early, the operator may explore the region of the primary operation, sep- arating bands of adhesions or kinks and relieving the obstruction. If jejunostomy is considered necessary, a No. 10 English catheter is inserted a few inches into the lining of the selected gut and fi.xed to the bowel bj' a purse-string suture of chromic catgut or silk. The catheter is then depressed into the wall of the bowel, which is sutured over it for an inch and a half. It is passed through a perforation in the omentum and brought out through the incision, sutures being passed through the peritoneum, the omentum, and the intestine on each side of the tube. In the larger number of a series of 43 cases the operation was necessi- tated by cancsr, and was palliative. Twelve of the patients died within a week, and 4 more within a month, but in all cases the operation served its purpose of affording temporary or - permanent relief. C. H. Mayo (Jour- nal-Lancet, Dec. 15, 1917). Surgery of the Appendix. — The vermiform appendix, while nomi- nally a portion of the colon, is subject to peculiar affections which, in them- selves often trivial, are prone to give rise to the most serious surgical com- plications. The mere removal of the appendix makes up a small portion of the actual surgery of this organ, which includes the surgical manage- ment of appendix-abscesses, appen- dix-peritonitis, and other complica- tions. Hence the description of appendectomy as a t>^pical operation representing the surgery of the organ is a small part of the subject, and re- quires elaboration only because of the different complications surrounding the work. The typical operation in a case of early infection, or in fibroid degener- ation of the appendix, consists in bringing the appendix to the outside of the abdomen, ligating it like an artery with catgut at two points, one- fourth inch apart. We sever the appendix between these two points of ligation and carry a drop of 95 per cent, carbolic acid into the lumen of each stump. The scissors or knife with which the severing is done is not used again at the operation, because the instrument is now infected, and is to be put aside in a safe place. The carbolic acid has sterilized the tissues with which it has come in contact instantly, and in order to stop any further and undesirable action we neutralize the carbolic acid with a few drops of alcohol applied with a pledget of cotton. The next step is ligation of the mesappendix with catgut at as many points as desirable in any particular case. In some cases the mesappendix allows a safe ligation with a sinHe ligature. In other cases where it has a particularly broad attachment, four or five ligatures may be required. It is quite as important in ligating mes- appendix as in ligating broad liga- inent after an operation for ovariot- omy, not to include too much tissue in any one ligature, and not to cut the stumps too short above the liga- ture, for the reason that vomiting and 80 ABDOMEN, SURGERY OF (MORRIS). other movements subsequent to the operation are particularly apt to force off these ligatures and give rise to secondary hemorrhage or opening of the lumen of the appendix. The last step after cutting away the mesap- pendix consists in scarifying the peritoneum of the cecum near the stump of the appendix that is left, with the point of a needle, in order to insure an abundance of lymph exuda- tion which will wall in the stump. The author has employed practi- cally all of the fanciful methods of treatment of the stump which have been described by authors, and has dropped all but this simple method, which saves time. At one hospital where four thousand appendectomies performed by this method have been tabulated, there were only two cases of trouble due to the form of pro- cedure, and both of these were due to the slipping of a ligature, both liga- tures having been tied by the same member of the house staff, who may not have learned to tie square knots, or who may have cut stumps too short. Where old adhesions make it difficult to bring the appendix out upon the abdominal wall, this simple method of treatment of the stump does away with many difficulties. In cases of acute infection with abscess, with dense new or old adhe- sions, it is extremely unwise to at- tempt to bring the cecum to the surface in order to carr}- out peculiar methods of treatment of the stump of the appendix, and in such cases it will suffice if we snap a pair of forceps upon the appendix close to the cecum, and remove the appendix with the finger without further detail, unless one wishes to leave another pair of forceps on the mesappendix. The forceps left in place for twenty-four hours serve to protect also the small drain placed alongside. At the end of twenty-four hours the forceps may be removed, and no more attention given to the stump of the appen- dix. In these far-advanced cases the arteries of the mesappendix have commonly been occluded by pro- liferating endarteritis and the veins are filled with thrombi, so that the hemorrhage amounts to nothing more than a moderate degree of oozing cared for by the capillary drain. Such simple treatment does away with a great part of the dangerously severe part of operative work which in the third era of surgery has often been thought necessar}^ Treatment of abscesses and peritonitis of appen- dix origin is discussed under the general head elsewhere in the article. See also Appendicostomy and the article on Appendicitis in the second volume of this work. Analysis of 822 cases of appen- diceal operation at the Cook County Hospital, Chicago, between Novem- ber. 1912, and February. 1916. Of the 58 terminating in death, 17 showed general peritonitis at the time of op- eration, and should be considered as cases of general peritonitis. Deduct- ing them from the 58, the mortality is 4.98 per cent, for uncomplicated acute appendicitis. Of 445 patients operated on for simple acute appendi- citis, 5 died, a mortality of a trifle over 1 per cent. Of 266 patients op- erated on for acute appendicitis — sup- purative, gangrenous, perforating — with abscess, 6 died, a mortality of 2.2 per cent. Of 127 patients having gangrenous appendicitis without ab- scess formation: 7 died, a mortality of 5.5 per cent. Of the series, 150 cases occurred in children under 15 years of age. Of these. 138 recovered and 12 died, a mortality of 8 per cent. The following conclusions are drawn: ABDOMEX, SURGERY OF (MORRIS). 81 General peritonitis is still the most frequent complication of acute appen- dicitis. Drainage tubes, gauze, etc., should be removed gradually to avoid inclusions and subsequent spread of infection. Early operation means a low mortalit}\ Abscess formation may be considered evidence of resist- ing power on the part of the organ- ism. Fecal fistula, while compara- tively frequent and annoying, has little importance in increasing mor- tality. Abortion is not greatly to be feared if appendicitis occurs dur- ing pregnancy. P. F. Morf (Jour. Amer. Med. Assoc, Ixviii, 902, 1917). Report on local anesthesia in 60 operations for acute and chronic ap- pendicitis. Three-quarters of an hour before operation ji grain (0.016 Gm.) of morphine is given hypodermatic- ally, and usually repeated just before operation unless the patient is drowsy. A 1 per cent, novocaine (procaine) solution is used, to the ounce of which 20 drops of 1 : 1000 solution of epinephrin are added. The meso-appendix is injected as well as the wall layers. There was no mortality. The average time of operation was 22 minutes, the length of time being due to the waiting for action of the anesthetic on the sep- arate abdominal layers and mesen- teriolum. Postoperative distention was usually absent. The day follow- ing operation, the author gives pituit- rin 1 c.c. (16 minims), and one-half hour later a rectal irrigation or high enema. The average stay in bed was less than 7 days. The chronic cases usually left the hospital 2 or 3 days later. Recent adhesions could be sep- arated without pain; when dense, novocaine was injected. J. Wiener (X. Y. Med. Jour., Aug. 2, 1917). In single suture appendicectomy, advised by the author in pelvic oper- ations, the tip of the appendix is picked up in a clamp, and a long 16- to 18- inch suture carried through the clear triangular space at its base and tied, thus ligating the appendic- ular artery. The mesentery is then cut free, leaving a small stump. Con- tinuous with the appendix, at its base, is the longitudinal stria of the cecum. One-fourth of an inch from this base the needle is carried with a Lembert- Czernj' stitch as a fixation suture to prevent the ligature from slipping. The needle is now carried back and inserted through the mesentery be- tween the first ligature and the base of the appendix, and tied to the proximal end of the first knot. The appendix is clamped, cut, and the stump treated with carbolic acid and alcohoL Anterior to the mesentery and upon the lower portion of the cecum, running in the direction of the ileum, there is always a fascial fold, the fold of Treves. This is now picked up on the needle and carried over to the most dependent portion of the cecum, where it is fixed with a Lembert-Czerny suture and tied. This covers the stump of the appen- dix and completes the operation, re- quiring in all 5 or 6 minutes' time. A. Walscheid (X. Y. Med. Jour., cvii, 8, 1918). Reviewing the opinions of sur- geons on Lane's theories as to the causation of intestinal stasis, and the results thereof, the writer concludes that although there is certainly an element of truth in Lane's theories and practice, his operative pro- cedures were altogether too radical. In his opinion surgery of the large intestine must be limited, with few exceptions, to cases showing definite evidence of obstruction. Ileosig- moidostomy should be cast aside as an operation of election, resection being the ideal procedure. In fact Lane is said to have discarded ileo- sigmoidostomy in favor of resection. Side by side anastomoses are un- satisfactory, as demonstrated by the frequency with which diverticula de- veloped in the blind end. End-to-end anastomosis gives the most satisfac- tory results. G. L. McGuire (Trans. Can. Med. Assoc; X^. Y. Med. Jour., July 13, 1918). Colostomy. — Now and then it be- comes necessary to perform colostomy 1-6 82 ABDOMEN, SURGERY OF (MORRIS). for patients suffering from chronic ob- struction induced by a growth, stric- ture, angulation, adhesion, volvulus, invagination, foreign body, diver- ticulum, or enteroptosis, after other measures have been tried and failed. Again, an artificial anus is sometimes made to relieve patients suffering from membranous catarrh, the various types of ulcerative colitis and mul- tiple polypi, but this procedure is not so popular for this purpose as it was before the advent of appendicostomy and cecostomy. An artificial anus should never be made except as a dernier ressort be- cause of its unnatural location, the odors which emanate from it, the necessity of wearing a bandage, and, further, because a serious operation is required when the time for its closure arrives. An artificial anus may be tem- porary when made as a preliminary step to excision and resection or until such time as the condition, for the relief of which it was made, has been cured; or permanent, when the open- ing is to remain through life. It is not necessary to spend as much time in the formation of a tem- porary anus as it is in the making of a permanent anus, because the former is to be of short duration and the patient can bear the annoyance for a short time. In permanent colostomy it is of the utmost importance to pro- vide for the patient's comfort by making the opening in such a way as to avoid painful evacuations, com- plete fecal incontinence or procidentia. Formerly there was considerable discussion as to which was the better procedure, inguinal or lumbar colos- tomy ; but lately the latter has fallen completely into disuse because the operation is more difficult, a suitable spur cannot be made, and the anus is situated where the patient cannot easily attend to it, while the former operation is devoid of all of these dis- advantages. Except where there are special reasons for doing otherwise, the colonic aperture should be made of fair size and as low down in the bowel as possible, because here the feces are more solid and give less trouble than when the anus is estab- lished at or near the cecum. An anal opening should never be made in the small bowel because when this is done there is a constant discharge of fluid tlirough it, which annoys the patient and keeps the skin continually excoriated. The majority of surgeons concen- trate their efforts toward the forma- tion of a proper spur and the produc- tion of the double-barrel-gun effect, to prevent any of the feces from reaching the rectum, but do compara- tively little toward providing an anus over which the patient can exert a fair degree of control. G ant's Colostomy. — The sigmoid is reached and isolated through a two- inch incision which crosses a line ex- tending from the umbilicus to the an- terior superior spine of the ileum, at the inner border of the oblique mus- cles ; working outward, the transver- salis is separated from the internal oblique muscle, with the index and middle fingers, for about one and one- half inches. The fingers are then forced upward through the oblique muscles and then over the external oblique and inward to the incision, separating the subcutaneous fat from the muscle. A loop of the sigmoid is now hooked up and then made to traverse the ABDOMEN, SURGERY OF (MORRIS). 83 route taken by the fingers, which occasional application of 6 per cent, makes it pass outward between the silver nitrate. When the obstruction internal oblique and the transversalis is located above the sigmoid, the st«ps muscles, and then through the in- in the operation must necessarily be ternal and external obliques and modified to meet the indications, but finally over the latter back to the the changes in the technique will incision. Again, when it is sutured suggest themselves to the surgeon in after being made taut to avoid the individual cases. possibility of subsequent procidentia, Patients have but little control the angles of the wound are approxi- over an artificial anus for the first mated by two chromicized catgut few days, no matter what operation sutures, which pass through the skin is performed, because the soreness of and fascia on one side of the incision the wound and the irritability of the and then beneath the longitudinal intestine excite frequent and strong band of the sigmoid and out through peristalsis and the involuntary dis- the same structures on the other side, charge of the feces, where they are tied. After the gut This procedure has the advantage has been attached to the skin by a over other colostomies in that but one few plain catgut sutures it is sur- incision is made and, further, because rounded by a bird's nest dressing it gives the patient a more perfect to prevent its being pressed upon, control over the movements than do covered with rubber tissue lubricated other colostomies. with sterile vaselin to prevent stick- According to Gant, patients oper- ing of the gauze to the bowel, and ated upon in this way except during then the outer dressing and binder the first few days rarely complain are applied. of the involuntary escape of gas and The intestine is not opened until ordinarily do not have an evacuation after the third day, except when there until they have taken a mild laxative is a marked distention ; under such or stimulated peristalsis by a small circumstances it is punctured at any enema. time after six ho\irs and amputated It requires very little time to later. The projecting piece of gut is perform, colostomy for a patient and quickly and painlessly removed by the operation is practically devoid of injecting a small quantity of a one- danger, but the reverse obtains in the eighth per cent, eucain solution into operation for its closure, as usually its mesentery. Cutting of the bowel done by intestinal anastomosis, proper causes no pain and does not To avoid the dangers which accom- require anesthetizing. pany joining of the two ends of gut, By a few cuts of the scissors, the Gant has devised a special plan for intestine is amputated about one- closing artificial ani. Some years ago quarter of an inch from the skin, he invented a clamp, which has bleeding points are ligated en masse, proved useful in the closing of colos- and hemorrhage from oozing surfaces tomy openings. Its weight is imper- is controlled by hot-water compresses ceptible to the patient, and when in or the cautery. The raw edges left place the shank, which is bent at an are encouraged to heal rapidly by the angle to the clamp, lies flat upon the 84 ABDOMEN, SURGERY OF (MORRIS). abdomen. The jaws are fenestrated, one-half inch broad and one and one- fourth inches in length. It is applied as follows : The clamp is placed in the applicator forceps, which are so adjusted that the jaws of the clamp remain open to the fullest extent. The parts having been cleansed, the partition between the upper and lower colostomy openings is stripped to dislodge any coil of the intestine which might otherwise be injured. The writer describes the following method calculated to insure sphincteric control after colostomy. The rectus is split vertically and the sigmoid is drawn out and divided at a convenient point. The lower segment is closed and replaced in the abdomen. The upper segment is made less bulky by removing the appendices epiploicae and freeing it of mesenteric fat, but with- out in any way interfering with its blood-supply. The artificial sphincter is then made in the following manner: A loop of muscle-fibers is separated Operation for sphincter control after colostomy. (Kyall.) (Clinical Journal.) The clamp is then applied, one blade in each opening, and pushed down sufficiently to include the entire spur, when it is released from the instru- ment. It is allowed to remain in situ until the spur is divided and it comes away unaided, which is usual!}' from six to nine days later. The clamp causes slight soreness, but no acute pain. To avoid complications, the patient had best remain quietly in bed until it sloughs out. When the partition has been successfully de- stroyed the skin and edges of the opening are freshened under local anesthesia and closed with catgut or silk, and, in case there is considerable tension, the wound is supported by well-adjusted adhesive straps. from the posterior aspect of the rectus on either side of the wound. Each loop is then drawn over to the opposite side of the wound, so that one loop over- laps the other. The overlapping loops thus form a ring and through this the bowel segment is drawn. Sutures are then inserted to keep the muscle- fibers together above and below where the bowel comes through. Anchoring stitches are inserted through the skin and muscle inside to keep the bowel in position. The wound is then closed above and below the bowel, and the cut edges of the latter are sutured to the skin. A double sphincter is thus formed consisting of longitudinal and circular fibers. The longitudinal fibers are those of the anterior portion of the rectus, and the circular fibers are formed by the loops from the posterior part of the rectus. This operation can be modified by making double loops on each side and making them overlap one ABDOMEN, SURGERY OF (MORRIS). 85 another alternately. A similar opera- lerior superior iliac spine, but the exact tion can be, and has been, carried length and location of the wound de- through the external oblique, and like- , „ \ ^ ..x ^ r i * , , , .1. t, 1 pends somewhat on the amount of sub- wise can be done wherever the bowel is brought through muscle. A some- cutaneous fat present. Through this what similar operation can be per- incision the fingers explore the abdom- formed for gastrostomy and appendicos- inal organs and the type and limitations tomy. C. Ryall (Clinical Journal, Nov. ^f ^^g stricture or tumor are learned. The sigmoid flexure, be it well devel- Lilienthal's Colostomy. — The for- oped or not, is drawn out. As is well mation of an artificial anus for the per- known, this part of the intestine varies manent relief of obstruction of the greatly in length, but all is taken out lower bowel is regarded by most sur- which can be withdrawn without ten- geons as a loathsome makeshift for sion. The two legs of the loop are the prolongation of life. The mental separated as widely as possible, the picture of such an opening suggests the upper leg being sutured to the perito- constant uncontrollable discharge of neum and posterior rectus sheath in the feces and flatus, the painful and an- upper angle of the wound, and the noying dermatitis in the neighborhood lower is sutured in a similar manner to of the exposed mucosa, and the neces- the inferior angle. Silk or linen thread sity for constant change of dressings — is the suture material, and the stitch- in short, a condition of actual and per- ing is done by the continuous method, manent disability for the ordinary every third stitch being tied so as to duties and pleasures of life. avoid purse-stringing. The mesosig- For a number of years Lilienthal has moid is now sutured through and been performing an operation which through to the peritoneum on each side obviates nearly all the discomfort and (Fig. 1 in the annexed plates), filthiness of colostomy. The patients At the lower leg of the loop the gut have absolute control of the bowels and is doubly ligated very tightly with can even hold a considerable quantity heavy silk or cotton twine. Section is of fluid injected into the colon. The carefully made between the ligatures, bowels move once 'or twice a day, the taking care to avoid soiling from the patient knows when the movements are small amount of imprisoned intestinal about to occur, and — not by any means contents. Pure carbolic acid on a gauze the least advantage — he is not annoyed sponge is used to sterilize the mucosa, by the necessity for wearing an appli- Chain ligatures of catgut or silk are ance for obturation. The operation has now passed through the mesosigmoid been tested many times, and the pa- so as to prevent hemorrhage, and this tients have been for the most part membrane is then cut across. We now carefully followed up. A description have a short piece of sigmoid, the dis- of the steps of the operation follows : — tal leg of the loop in the lower angle An incision about 3V2 inches long, of the wound, and a long piece sutured more or less, is made over the outer in the upper angle of the wound. The third of the left rectus muscle and par- remainder of the mesosigmoid is cut allel with its fibers. The upper end of away from the long piece of intestine, this incision is just about on a line be- freeing it completely. The entire tween the umbilicus and the left an- wound is now protected by gauze pack- 86 ABDOMEN, SURGERY OF (MORRIS). ings, the peritoneum by our previous one, is now inserted about six inches procedures being entirely closed off into the intestine and is tied in place, a by suture. We should have about 3 or single light suture passing through its 4 inches of free sigmoid at the upper walls guarding against its accidental angle of the wound. If there is more extrusion. The remainder of the it should be ablated. Four equidistant wound is left open and packed with clamps are now placed at the edge of gauze while the tube is led off into a this upper piece of intestine ; the gloved receptacle at the side of the bed. These finger is inserted into the lumen of the wounds always become more or less gut to the place where it is held to infected, out I have encountered a true the peritoneum by suture ; an assistant phlegmon only once and then a single rotates the clamps so as to twist the incision sufficed for its drainage, gut around its longitudinal axis, after About a week after the operation the the manner described by Gersuny, tube may be withdrawn and the re- from 180 to 360 degrees according to dundant sigmoid burned off with the the texture and thickness of the walls actual cautery. Anesthesia is not nec- of the sigmoid with which we are essary. Even then it will be found that working. By withdrawing and rein- repeated cauterizations will be re- serting the finger from time to time quired during the course of the heal- the degree of constriction which this ing in order to bring the intestinal maneuver produces may be accurately mucosa to the skin level. Daily irri- gauged. When this seems to be suffi- gations through the tube should be cient for the purpose — a matter of in- practised so as to keep the patient's dividual judgment — a few interrupted bowels open. The string around the silk or linen sutures passed through lower jiiece of intestine should be re- the visceral peritoneum and sub- moved in three or four days; other- mucosa to the aponeurosis of the exter- wise, there might be danger of com- nal oblique hold the rotated gut in j)lete and permanent closure, and it is position. It is now necessary to make necessarv' to maintain patency here sure by re-examination that a suffi- for the sake of drainage, cient twist has been accomplished. If The control of the bowels is learned this seems satisfactory more sutures gradually by the patient, and he is as- should be put in to hold the gut firmly sisted by a constipating diet and, for to the aponeurosis. the first few weeks, small dosqs of In examining with the finger now deodorized tincture of opium and of we find a double sphincter, the first subgallate of bismuth, 20 grains three one at the twist; the second, more an to five times a day. It takes about a angulation than a sphincter, at the month for the final result to be at- point of peritoneal fixation. A few tained. but the functional result in all chromic gut sutures close the portion uncomplicated cases will be found of the remaining wound in the aponeu- perfect. rosis. The sphincteric action is main- The writer employs one of the fol- taned by the fibers of the rectus l«>^i"- procedures: (1) Sigmoid 1 11 I, xu ^ • ^ • a.1 above the stricture joined to the muscle as well as by the twist m the , , . r . /o^ -r -'. sound lower part of rectum; (2) it mtestme. A large-sized, rather stiff- sigmoid fixed, transverse colon, if walled rubber rectal tube, not a woven low, anastomosed to the rectum and The Dotted Line Shows Line of Section. The Bhint Retractor Holds Outer Third of Rectus Muscle Together with Skin and Aponeurosis. (Hoivard Lilietithal.) Annals of Surgery. Redundant Bowel and Mesocolon Cut Away. Twisting of the Intestine Begun. (Hozi'ard Lilienfhal.) Annals of Surgery. Twist Complete and Maintained in Position by Anchor Sutures Holding Sigmoid to Aponeurosis. {Howard Lilicnthal.) Annals of Surgery. Operaiion Complete. Aponeurosis Further Stitched to Intestine and \\'ound Closed with the Exception of the Skin. {Howard Lilienthal.) Annals of Surgery. ABDOMEN, SURGERY OF (MORRIS). 87 to the descending colon above stric- ture; (3) cecum joined to rectum and the ileum to colon above stricture; (4) lowest coil of ileum. joined to the rectum and bj' a lateral anastomosis to the descending- colon above the obstruction. In the upper opening the small female end of a Hildebrand button is inserted and fixed with a purse-string suture. With special forceps the larger male end is passed through the rectum and made to project up- ward, so that a small incision may be made over the central part, which then protrudes, allowing the bowel wall to slide down so close to the spring that no suture is needed. The 2 halves of the button are then clamped. The result is a passage for fecal matter into the rectum instead of outward on the abdomen. McArdle (Pract., June, 1916). The indications for colostomy are given by the writer as follows: (1) As a preliminary to excision of the rectum for cancer. (2) To prolong life and prevent obstruction in inop- erable cancer of the lower bowel. (3) In all cases of pericolitis of the lower part of the pelvic colon where resection or short-circuiting is im- possible. (4) In some cases of in- tractable ulceration of the rectum. (5) In intractable fibrous stricture of the rectum. (6) As a temporary measure in severe wounds of the rectum. Referring in particular to trans- verse colostomy, he points out cer- tain advantages of this procedure. It seems to afford better control over the stools than sigmoid colostomy, and prolapse is much less common. In performing transverse colostomy, the colon should not be opened at the most dependent part but as near the splenic flexure as is possible without causing tension. When the trans- verse colon is short, sigmoid colos- tomy should be preferred. The colon should subsequently be cut com- pletely in half to arrest the peristaltic wave at the opening. Lockhart- Mummery (Practitioner, Aug., 1917). Appendicostomy and Cecostomy. — These operations are useful in the treatment of disease located in the colon, but, when the disturbance lies within the small bowel or involves it and the large intestine, Gant's cecos- tomy, which provides a means by which the treatment can be directly applied to both, should be substituted. It is frequently impossible to deter- mine whether the disease is limited to the colon or not, and because of this and the fact that this operation is no more difficult or dangerous than appendicostomy and ordinary cecos- tomy, and is equally effective both when the lesions are located in the small intestine, the large bowel or both, Gant believes his to be the most desirable procedure. Appendicostomy. — Some surgeons do not open the appendix during the operation because they fear infection. This practice, Gant believes, is bad except when it is obviotis tliat the appendix is not obstructed, because he has encountered three failures fol- lowing it ; in one the appendix was too short, in another it was strictured, and in still another it was blocked by an encysted grapeseed. He immediately amputates the ap- pendix and introduces the probe- pointed appendiceal irrigator, then nothing can interfere with postoper- ative irrigation, but when the appen- dix is diseased it is removed and cecostomy is performed. It is impor- tant that the irrigations be started at once when patients suffering from ulcerative colitis are despondent, greatly debilitated, have many move- ments, lose considerable blood, and suffer from insomnia and autointoxi- cation. To meet these conditions Gant has 88 ABDOMEN, SURGERY OF (MORRIS). devised a technique for appendicos- tomy which provides for irrigation both during and following the opera- tion, since the adoption of which his patients have gained ver>' much more rapidly than formerly, when the ap- pendix was not opened for several days, during which time nothing was done to relieve them. Now and then a stitch abscess has occurred, but other complications have not arisen during or following the operation. Briefly described, the following are the steps: 1. The appendix is ap- proached through a gridiron incision and located by tracing the anterior longitudinal band downward, when it and the cecum are freed and brought outside. 2. The cecum is drawn first to one side and then the other by an assistant, while the parietal perito- neum is removed at the sides of the incision to insure union between it and the transversalis fascia, or the peritoneum is left intact when the gut is to be brought into contact with it. 3. The appendix is freed and straightened by ligating and dividing adhesions and the mesentery- at about one-fourth inch from it. 4. After the cecum has been scarified, two sero- muscular suspensor}^ sutures are in- troduced on either side and near the base of the appendix, each taking three bites in the gut. 5. By means of a strong, long-handled needle, the anchoring stitches are in turn carried through the entire thickness of the abdomen and clamped with forceps, but when the intestine is joined directly to the peritoneum the bowel is anchored by chromicized gut su- tures, including the parietal perito- neum and transversalis fascia. 6. Having surrounded the appendix wnth gauze, a traction suture is introduced to steady it while it is being ampu- tated, cauterized, and probed. 7. A Gant appendiceal irrigator closed with a stopper is introduced and the ap- pendix ligated above it. 8. The ap- pendix is placed in the lower angle of the wound, pointing upward to prevent leakage later, and anchored by two seromuscular chromicized-gut sutures, which include the trans- versalis fascia. 9. The abdominal layers are then separately approxi- mated by interrupted or continuous stitches, after which the cecal sus- ])ensory sutures are tied across rubber tubes. 10. The appendiceal irrigator is prevented from slipping out by the adjustment of adhesive straps or by means of attached pieces of tape which encircle the body. 11. In urgent cases from one to three pints of warm saline solution are imme- diately injected into the colon, when the stopper is introduced to prevent leakage. 12. The wound is sealed by means of cotton and collodion, and is protected further by split gauze pads which overlap each other when placed about the appendix. 13. The outer end of the irrigator is surrounded by twisted gauze strips to prevent pres- sure upon it when the outer dressings composed of gauze pads or cotton and a many-tailed binder are adjusted. In gastro-intestinal perforation fol- lowed by acute peritonitis, the writer noted that the nausea, vomiting, and cardiac and pulmonary symptoms due to paralysis of the intestine, cease after appendicostomy, normal peristalsis being, moreover, re-estab- lished. The fluid introduced through the appendix by the drop method is quickly absorbed and nothing need be given by mouth until normal con- ditions are restored in the intestine. After 12 hours, the fluid discharged by rectum is usually colored with bile, ABDOMEN, SURGERY OF (MORRIS). 89 showing intestinal paresis has been overcome. Appendicostomy does not prolong the major operation more than 2 or 3 minutes. The absorption of water prevents shock and causes rapid detoxication by washing out the large intestine; siphonage of the small bowel is also effected. The writer reports 10 cases, in 1 of which the bowel had been perforated in 8 places by a bullet. Two patients had been run over. Most of the other cases were perforated gastric ulcers. The appendicostomy gave results not obtainable by any other procedure. J. Roux (Rev. med. de la Suisse Rom., XXXV, 814, 1915). Appendicostomy has the advantage over cecostomy in that there is no discharge of feces or gas. A woman who had suffered over 14 months from bloody diarrhea was sent to a hospital with a diagnosis of tubercu- losis of the intestines. An explora- tory laparotomy having disproved this, and colitis been found, appendic- ostomy was performed. Enemas of salt solution were then given by the drop method, and later drop enemas of 1 to 2 per cent, tannin solution 3 times daily. There was prompt im- provement and after 2 months com- plete recovery. The drop enemas were continued by the patient her- self. After a recurrence from neglect the fistula was dilated with a laminaria tent and the treatment resumed. The patient then recovered completely. Hans Brossmann (Med. Klinik, Sept. 1, 1921). Appcndicocecostomy. — On a number of occasions Gant has been com- pelled to abandon appendicostomy for cecostomy because the appendix was too short, strictured, or blocked by a grapeseed which rendered it unfit for irrigating- purposes or had sloughed off following appendicos- tomy. In each instance, after the appendix had been amputated or inverted, a catheter was introduced through the appendiceal stump or opening and fastened by a purse- string suture introduced at or near its base. The cecum was suspended and the rest of the operation performed as in appendicostomy. Two patients suffered from diar- rhea induced by ulcerative lesions in the colon. In these cases the catheter was introduced a short way into the cecum, providing for colonic irrigation. The others were afflicted with enterocolitis, and it was thought ad- visable to irrigate both the large and small intestines. This was accom- plished by guiding a catheter across the cecum through the ileocecal valve into the small bowel. This procedure is termed "appcndicocecostomy." The principal objections to this operation are (1) that a change of catheters is impossible because the appendiceal and ileocecal openings are nearly on the same level, and (2) because the appendiceal aperture is so small that two catheters of suffi- cient size cannot be introduced to provide for large and small bowel irrigation. Cecostomy. — Experience has dem- onstrated to Gant's satisfaction that cecostomy is preferable to appendi- costomy in the direct treating of intestinal disease. A comparative study of the advantages of cecostomy and the disadvantages of appendicos- tomy, as enumerated below, will show why the former should take prefer- ence over the latter. The advantages of the cecostomy operation, and more especially the writer's cecostomy, which provides a means of irrigating both the large and small intestine, are: 1. Owing to the fact that the cecum lies against the inner abdominal parietes. it can be easily anchored without angulating 90 ABDOMEN, SURGERY OF (MORRIS). or twisting the bowel. 2. Since the opening is opposite the ileocecal valve, a catheter can be introduced into the small bowel for irrigating purposes or the siphoning of its con- tents for examination. 3. The cecal opening can invariably be made of a suitable size. 4. The circular, valve- like projection formed around the catheter by the infolding purse-string sutures prevents leakage. 5. The catheter can be changed without diffi- culty. 6. Closure of the opening fol- lows withdrawal of the catheter and a few applications of the copper stick or cautery. 7. Owing to the natural position of the cecum, there is less tension and pain following its anchor- age to the abdomen than occurs after appcndicostomy. 8. This cecostomy may be employed in the treatment of lesions located anywhere in the intes- tinal canal, while appcndicostomy is limited to those in the colon. The disadvantages of appcndicos- tomy are the following: 1. The ap- pendix is more difficult to bring up for anchorage than the cecum because of its deeper and more uncertain position, and because it is frequently bound down by adhesions or a short mesentery. 2. Anchoring of the ap- pendix causes angulation or twisting of tlie cecum, which, in turn, may induce constipation, discomfort, or pain. 3. \Mien the cecum about the appendiceal base is caught in the wound, it induces nausea and vomit- ing until detached (writer's case). 4. When the appendix is small, short, strictured, bound down by adhesions, blocked, or is otherwise diseased, it is useless for irrigating purposes. 5. Irrigation is frequently difficult and unsatisfactory because of the small appendiceal opening. 6. Pain follow- ing appcndicostomy is much greater than after cecostomy owing to the pulling upon the appendix by the loaded cecum, the periappendiceal adhesions, or the squeezing of the attached mesentery when the wound is closed tightly about it. 7. Fre- quent dilatation or the insertion of a catheter is often necessary to keep the opening sufficiently large. 8. Death has followed injection of the irrigating fluid into the abdomen beside the appendix w^here an interne mistook an opening in the wound for that of the appendix. 9. After a cure it is more difficult to close the ap- pendiceal than the cecal outlet, and frequently appendectomy is impera- tive. 10. Appcndicostomy frequently fails because the appendix slips back into the abdomen or retracts suffi- ciently to make irrigation almost or quite impossible. 11. The appendix has been known to slough off on several occasions owing to tension, its constriction by the sutures or destruc- tion of its blood-supply making subse- quent cecostomy necessary. 12. Appcn- dicostomy is not efifective when the disease is located in the small intes- tine. 13. Appendicitis requiring ap- pendectomy following closure of the appendiceal outlet has occurred. 14. Owang to the irritation caused by the catheter or treatment the mucosa may become so inflamed and swollen, ulcerated or strictured, that irrigation must be abandoned. 15. Finally, ac- cording to Reed, the catheter causes the wall of the appendix frequently to perish in a few days. Cecostomy zvitli an Arrangement for Irrigating both the Small Intestine and Colon. — Gant has described what he believes to be an original way of irri- gating both the small and large bowel ABDOMEN, SURGERY OF (MORRIS). 91 through the same opening in the cecum — an operation which, for want of a better name, he has designated "cecostomy with an arrangement for irrigating both the small intestine and colon." He believes his cecostomy is su- perior because the technique is simple, the operation requires no more time than others, there is less leakage owing to the purse-string infolding being substituted for his lateral sutures, both the small and large bowel can be irrigated by the attendant or patient, a firmer support is obtained by attaching the cecum to the transversalis fascia than to the parietal peritoneum, and the opening heals spontaneously after the cathe- ters are removed. Briefly described, the steps in Gant's cecostomy are: 1. Through a two-inch intermuscular incision made directly over the cecum, it and the lowermost part of the ileum are withdrawn and the edges of the wound covered with gauze hand- kerchiefs. 2. The anterior surface of the cecum is scarified after the as- cending colon and ileum have been clamped to prevent soiling of the wound when the bowel is opened. 3. Four linen seromuscular purse-string sutures are introduced into the an- terior wall of the cecum opposite the ileocecal valve, and the bowel is opened inside the suture line. 4. The gut is grasped at the juncture of the large and small intestines and held in such a way that the ileocecal valve rests between the thumb and fingers of the left hand. A Gant catheter guide is then passed directly across the cecum and through the ileocecal valve into the small intestine, aided by the thumb and fingers. 5. The guide is held by an assistant while the obturator is removed and a cathe- ter is introduced into the small bowel. It is then removed and the catheter firmly held in the small gut by an assistant until anchored to the cecum by catgut sutures to prevent its slip- ping out during the operation. 6. A short rubber tube three inches long is projected into the cecum for an inch or more and anchored beside the one in the small gut. 7. The infold- ing purse-string sutures are now tied, forming a cone-shaped valve above the catheters to prevent leakage of gas and feces. 8. After removal of the clamps, the cecum is scarified and anchored to the transversalis fascia, denuded of its peritoneum by through- and-through suspension sutures of linen, or by chromicized catgut stitches, including the fascia, when the two peritoneal surfaces are to be approximated. 9. The wound is closed by the layer method and the catheters are fastened by stitching or by encircling them with an adhesive strip to hold them together, and crossing this at a right angle with a second piece of plaster placed be- tween the catheter to prevent their slipping out. 10. The ends of the catheters are closed with cravat clamps to prevent leakage, and the operation is completed by applying the dressings above the projecting tubes. One catheter is left longer than the other or is identified in some way in order that the interne or nurse may know zvliich is in the large and zvhich in the small intestine when time for irrigation arrives. To avoid danger from infection treatment is not begun before the fifth day except when urgent. 92 ABDOMEN, SURGERY OF (MORRIS). The catheter may be readily in the small intestine and the latter changed by cutting the attached ad- could be removed and replaced with hesive strips and withdrawing" the a new one at will, and, further, (rf) one projecting into the cecum. Gant's fluid feces could be withdrawn more catheter guide is then passed over quickly and frequently through the the other into the small intestine, pipe in the small intestine than where it is retained until the old tube through the colonic catheter, has been removed and a new one in- To avoid possible expulsion of the troduced. A second piece of catheter catheter from the ileum, catheters is then placed in the cecum and both made of silk, silver, glass, and soft are prevented from slipping out by rubber reinforced by an inner metal adjusting fresh adhesive straps after tubing w^hich cannot be forced out of the manner already described. the bowel owing to their non-flexi- Before 'deciding upon the above bility are employed. Only that technique Gant irrigated tiie small portion of the latter projecting into intestine by passing a glass or silver the small bowel was reinforced, and catheter through a cecal opening, past as a result it served the desired pur- the ileocecal valve, into the small gut pose and caused but little irritation each time it was irrigated, but this because it was soft and flexible. This practice was abandoned as impracti- cecostomy permits the attendant or cable because of the difficulty en- the patient to irrigate the small and countered in locating and passing the large intestines at will, and the fluid valve, and, further, because the may be siphoned or allowed to escape patient could not irrigate himself in through the anus and the catheter this way. can be changed quickly as often as is Gant has had no reason to suspect necessary, that peristalsis forced the catheter Entcrocolonic Irrigator. — An instru- out of the small intestine into the ment successfully employed by Gant cecum except in one of his first a number of times in direct treatment cecostomies, where the tube was cut of intestinal affections involving both short and projected only one inch the large and small intestines. It is beyond the ileocecal valve instead of made both of rubber and metal, several, as it should. He feels confi- When it is in position, the attached dent that the catheter remained in inflating bag lies in the small intes- the small gut in his other cases be- tine at or near the ileocecal valve, and cause (o) water injected through the when distended prevents the escape colonic pipe was evacuated much of the solution into the cecum, there- quicker than when it was deposited by enabling the attendant to accu- in the small bowel ; {h) when a rately gauge the amount of fluid minute quantity of a 10 per cent, deposited in the small bow^el and to solution of methylene-blue was in- retain it there as long as required, jected through the former, it appeared By means of this twin-tube irrigator, in the urine more quickly than when the small and large intestines can be introduced through the catheter in quickly and scientifically flushed, the small gut. and (c) the catheter singly or together, by the physician, guide could be carried over the tube nurse, or patient. ABDOMEN, SURGERY OF (MORRIS). 93 The steps in cecostomy, when the irrigator is employed, are similar to those already described when separate catheters are used, except that the Gant catheter guide is unnecessary and the apparatus is retained in posi- tion by attached pieces of tape which encircle the body. Indications for Direct Bozvel Treat- ment.— This form of treatment has a wide field of usefulness. Most physi- cians and surgeons appear to labor under the impression that it is limited to the colon and is indicated only in ulcerative lesions of the large bowel causing diarrhea. Gant has called attention to the fact that this type of cecostomy is indicated in the treatment of intesti- nal parasites, enteritis, enterocolitis, and catarrhal, tuberculous, syphilitic, dysenteric and gonorrheal colitis ; ordinary and pernicious anemia; the many manifestations dependent upon intestinal autointoxication, ptomain poisoning, diarrhea of adults and children, intestinal feeding, malnutri- tion, and following operations upon the mouth, throat, esophagus or stomach ; in gastric stricture, ulcer, cancer and other disturbances where rest of the organ is indicated. Gant also called attention to the fact that by means of his cecostomy various intestinal diseases could be investi- gated, and that the procedure could be used to determine the amount and nature of the intestinal juices and dis- charges, the character of the feces, the action of salines and other cathar- tics injected directly into the small and large bowel, and the marked im- mediate vasomotor effect following hot and cold enteroclysis and many other interesting problems. Gant has also pointed out the use- fulness of appendicostomy and cecos- tomy as a means of drainage when the cecum or other part of the colon was excluded. He has also employed appendicostomy and cecostomy a number of times when operating for mechanical constipation where colitis was a complication, and also in the palliative treatment of obstipation where the patient declined to have the cause of the obstruction removed and yet suffered from marked autoin- toxication or recurring impaction. Gant and Reed have also performed cecostomy once for the relief of septic peritonitis. The latter recorded a case of "defective flora" of the colon which was improved by the injection of the needed bacteria through a cecostomy opening, and called atten- tion to its usefulness in the treatment of intussusception. Following direct treatment, the condition of the patient becomes rapidly better and manifestations such as anemia and those induced by autointoxication rapidly disappear, and in cases of diarrhea the frequency, of the stools generally diminishes and the amount of blood, pus, and mucous passed becomes markedly less. The good results following the irrigating treatment are due mainly to the mechanical action of the fluid in cleansing and stimulating the ulcers and removing retained toxins, and not to its temperature or chemical contents. Solutions should always be employed at the bodily temperature or warmer because of their soothing effect upon the irritated bowel, and not cold or at a freezing point, as recommended by some authors, be- cause when injected ice cold they excite enterospasm and cause much unnecessary suffering. 94 ABDOMEN, SURGERY OF (MORRIS). Briefly stated, the most reliable, stimulating, and soothing remedies to employ are weak solutions of boric acid, quinine, formalin, Hydrastis, krameria and soda, silver nitrate, and those of a soothing nature are kero- sene, liquid paraffin or olive oil, ac- cording to indications. The stimulat- ing solutions are used stronger when ulceration is extensive and the oils warm when the gut is irritable. Colectomy. — Excision of the colon is performed for malignant disease, including tuberculosis and gangrene, but in practice the operation, like colostomy, is confined to cecectomy and sigmoidectomy, unless the morbid process directly involves the trans- verse colon, V here the hepatic or splenic flexure is usually the seat of the disease. Of late, colectomy more or less ex- tensive, has been practised for severe chronic intestinal stasis. In colectomy for stasis the chief object is first to separate the evolu- tionarj' adhesions from the mesen- tery. The outer peritoneal aspects of the mesenteries should be left smooth. The ileum is divided usually within a few inches of its termination. The longer the small l)owel remain- ing, the greater the increase in weight after colectomy; in stout patients shortening of the small intestine is of material advantage. The pelvic colon is drawn up from the pelvis and grasped with forceps about 2 inches above the level of the pelvic brim, and the end of the ileum attached directly to the cut end of the pelvic colon. The innermost row of sutures perforates all the coats of the bowel, and is of the button-hole type, while the outer rows secure only the peri- toneal and muscular coats. Difficulty in anastomosis because of the differ- ence in caliber is met by arranging the sutures so that each picks up a correspondingly greater portion of the circumference of the pelvic colon than of the ileum. Finally, the cut edges of the niesentery of the ileum and pelvic colon are sutured together, care being taken to leave no raw sur- face. An esophageal tube is intro- duced through the rectum and ileo- colic junction. Lane (Brit. Jour, of Surg., Apr., 1915). Summarizing the final results of total colectomy for constipation: in only 6 of 12 cases operated could the result l)e considered entirely satisfac- tory. In all cases there was great improveinent in the constipation for a time, to be followed in 4 by a gradual recurrence, though in some cases not as severe as before. In no case was there diarrhea of long standing, nor undue thirst. In 6 cases there was marked improvement in nutrition. On the whole, total colectomy is justifiable only in severe cases of ob- structive constipation. The colec- tomy should be limited to the ascend- ing colon and the middle of the transverse colon, with lateral anasto- mosis of the ileum into the transverse colon. J. G. Clark (Surg., Gynec. and Obstet., May, 1916). In carefully selected patients with stasis who are toxic from their con- dition, the writer deems right-sided colectomy, with preservation of the omentum, justifiable. It gives as good results as general colectomj^ and has less primarj' and secondary danger. There is great variation in the length and size of the human in- testine. The shortest, 8 feet, is the carnivorous type; the longest, 33 feet, the herbivorous type. End-to-end union of ileum to colon is a safe pro- cedure. The closed end of the large bowel, being incorporated into the wound and brought through the peri- toneum, into but not through the muscle, may be opened to serve as a gas vent should the necessity arise. In most cases constipation is im- proved, but the best results follow operations of necessity for tumor and obstruction. Among 262 resections of the large intestine for malignancy, 54 per cent, of those who recovered ABDOMEN, SURGERY OF (MORRIS). 95 ■ were alive after 5 years, and 67.5 per cent, after three years. Among 235 cases in which the right half of the colon was resected for tumors, dis- ease and stasis, the operative mor- tality was 12.5 per cent. Mayo (Jour. Amer. Med. Assoc, Sept. 9, 1916). Right colectomy is followed by less unpleasant postoperative sequelse than total colectomy or ileosigmoidostomy, and is fully as satisfactory in reliev- ing stasis. Only such cases as have failed to be relieved by simpler measures are considered suitable for operation. In a postoperative X-ray study of 9 cases made for the purpose of de- termining whether the absence of an ileocecal valve had any effect on the emptying of the small bowel, it was found that in no case was there any damming back in the ileum or any evidence of dilatation of this portion of the bowel. The operation consisted in the re- moval of the last few inches of the ileum, cecocolon, and about a third of the transverse colon. In his earliest cases, he did not remove as much of the transverse colon as he did later, and postoperative X-ray ex- amination shows redundancy and ptosis of this portion of the colon, although the functional result was perfect. P. P. Johnson (Boston Med. and Surg. Jour.^ clxxvi, 266. 1917). The writer performed 15 total colectomies for constipation, with 1 death; and right colectomy for can- cer in 9 cases, with 2 deaths; for tuberculosis in 11 cases, with no deaths. For constipation a right hemicolectomy (the cecum, ascend- ing colon, and half of the transverse colon) is not so effective as a total colectomy. The operation onlj' re- lieves more or less, in a proportion dependent on the condition of the other organs. In the older total colectomy, the omentum was sacrificed. The writer holds that the omentum must be pre- served. But a total colectomy leaves irremediable and persistent abdominal disturbances, and Pauchet after 10 years' experience now does a right colectomy with preservation of the whole omentum. V. Pauchet (Presse med., Sept. 9, 1918). Series of 19 operations in which the right colon was excised for relief of symptoms which were attributed to blocking of feces in the cecum. The immediate result of the operation showed that it could be done without undue ris'<;: 20 cases reported by Mayo, 12 by Johnson, and this series of 19, without a mortality. It is, however, too serious to be under- taken except for very detinite condi- tions of incurable partial obstruction. The indications for excision are dila- tation of the cecum, extreme mobil- ity, presence of adhesions in patients unrelieved by any palliative treat- ment and whose symptoms lead to chronic invalidism. Brewster (An- nals of Surg., Aug., 1918). Cecectomy. — This operation, while so named, is by no means limited to the cecum, for it is usually necessar}^ to remove either the ascending colon or a portion of ileum or of both intes- tines together. Hence such interven- tion may be termed ileocolectomy, ascending colectomy, etc., according to the individual case. The incision is made in the middle line, unless the diagnosis has been made so well that the operator can incise directly over the growth. As in all similar cases, the gut is mobi- lized, brought out and walled off with gauze, while it is emptied and clamped or held empty by assistants' fingers or tape. The technique differs little from that of enterectomy of the small bowel. The mesentery is tied off and then divided, the large bowel excised and the operation completed by restoring the continuity of the intestine. As the cecum and ap- pendix have been sacrificed, it is necessary to secure an anastomosis 96 ABDOMEN, SURGERY OF (MORRIS). between the ileum and transverse or descending colon. An end-to-end anastomosis is hardly practicable because of the disparity in size between the small and large bowel. Hence a lateral anastomosis or an implantation is indicated, which may be made by suture or button. The technique is that usually pur- sued in all intestinal anastomoses. Lateral anastomoses are practi- cable when the ileum is to be united with the neighboring ascending colon. No attempt is made to provide for a cecal pouch or ileocecal valve, but the two ends are joined after the cut end of the colon has been closed. Tt is sometimes advisa.ble to im- plant the ileum in the descending colon or sigmoid flexure (ileosigmoid- ostomy). This would be necessary if the ascending colon were sacrificed. Sigmoidectomy, — As the sigmoid flexure is a favorite seat for cancerous growths it is often necessar\' to excise this portion of the bowel. In some cases no attempt is made to restore the continuity of the bowel, but the operation is terminated by forming an artificial anus. If, how- ever, the sigmoid is movable and the tumor can be removed cleanly, an end-to-end anastomosis may be made. Even when the rectum needs removal with the sigmoid, operators have pre- ferred to draw down the sound intes- tine and suture it to the anal region. In transperitoneal sig^moidotomj' the author seldom uses the exagger- ated Trendelenburg posture, and in old and adipose persons is especially cautious. The sigmoid is opened on the anterior longitudinal hand and the tumor exposed, drawn through, and double clamped. The growth is re- moved with the cautery and the de- fect closed from the mucous side by continuous sutures of chromic catgut after the method devised by Pilcher for the excision of hemorrhoids. It is covered on the peritoneal side with a few interrupted silk sutures. The incision in the sigmoid is then closed with continuous catgut and inter- rupted fine silk. A red rubber tube is now passed up into the sigmoid beyond the line of sutures and fastened with a catgut suture to the anus; this is left in situ for a few days to prevent gas pressure. The procedure described was found most efficient for growths similar to papil- loma. Mayo (Annals of Surg., July, 1917). In performing a three-stage opera- tion for cancer of the sigmoid, the writer at the first operation draws the loop of bowel containing the growth out of the wound as far as possible and keeps it there by a glass rod passed through the mesocolon or by a couple of stitches. Delivery of the colon is often facilitated by division of the external mesocolon. A glass tube is tied into the loop above the growth either at the operation or 36 hours later. After 10 days, the part of the loop external to the abdominal wall is cut off, generally without an anesthetic. There is no pain except some colic if the mesocolon is ligated. The final operation can be performed at any time after the wound has healed. In 2 out of 3 cases the writer made end-to-end anastomoses in the abdominal' wall without opening the peritoneal cavity. P. Lockhart-Mum- mery (Proctol. and Gastroenterol., xi, 80, 1917). SURGICAL AFFECTIONS OF THE PANCREAS.— These comprise inflammation, cancer, cysts and cal- culi. There are no typical operations for these afi"ections, or upon the pan- creas and its duct for any conditions. Acute Pancreatitis. — In this condi- tion the pancreatic juice escapes into the tissues of the pancreas and into the peritoneal cavity, and the eflfect of its irritating influence is very de- ABDOMEX, SURGERY OF (MORRIS). 97 structive. The reddish, purulent fluid in the vicinity can be removed by a drain, and tense parts of the pancreas can be scarified to allow some of the interstitial exudates of the pancreas to drain out. Drainage is essential after removing tumors, or after an injury to the pancreas in order to dispose of the irritating" pan- creatic secretion. The escape of pancreatic secretion from an injured gland reduces living fat in this vicinit}- into its fatty acid and glycerin, due to a ferment in the pancreatic fluid. The glycerin is absorbed and the fatty acid which remains makes a combination with lime salts, with the effect of produc- ing small areas of dull white at points where the reaction has taken place. Acute pancreatitis should be the occasion for prompt abdominal sec- tion for the severe and fulminating symptoms usually present, and emer- gency laparotomy would in any case be required. If the patients have not died outright of collapse or peritoni- tis, the fat necrosis or some other secondar}^ conditon will demand operation. In the ultra-acute and acute vari- eties of pancreatitis immediate opera- tion should be the rule, the prime object being early and adequate drainage. The best approach in this stage is by an anterior incision either through the gastrocolic omentum or the gastrohepatic ligament, depending on whether the stomach is situated high or low. The pancreas should be freely incised longitudinally, or num- erous blunt punctures made in its substance, thus giving vent to the blood, lymph, and obstructed secre- tions. Both gauze and tube drainage should be laid down to the surface of the organ and conducted to the surface through a sheet of rubber dam to minimize adhesions. The only ex- ceptions to the rule of immediate operation are severe shock and ob- vious improvement from the effects of the disease. In 13 operations for acute pan- creatitis, 3 cases resulted fatally; one of these was of the ultra-acute variety. Usually there is ample mar- gin of safety for the experienced ab- dominal surgeon also to open, empty,, and drain the gall-bladder and com- mon duct if necessary. J. B. Deaver (Jour. Amer. Med. Assoc, Ixix, 434, 1917). The pancreas may be reached either above or below the stomach, through a second incision into the omentum or mesocolon, after making a suitable external incision. A counteropening through the lumbar region may be necessary for drainage. If an abscess is still intact it should be opened wherever most accessible. The in- frequently, fatal character, and opera- tive mortality (chiefly unavoidable) do not justify us in devoting much space to abscess of the pancreas, the treatment of which largely resolves itself into management of the second- ary^ conditions to which it gives rise. Shallow incisions followed by simple wick drainage carried to the pancreas certainly serve to remove poisonous exudates to advantage in some cases of acute pancreatitis, and even the simple use of wick drains without scarification of the pancreas is some- times followed by good results. We must leave room when draining to allow necrotic masses to escape. Pancreatitis is, with few exceptions, an infective disorder, propagated in the majority of instances from the duodenum and gall-bladder, usually by the way of the lymphatics. Acute pancreatitis is usually infection plus ferment activity, though it may be traumatic or clinical exceptionally. In operating for acute pancreatitis. the diagnosis of pancreatitis is a 98 ABDOMEN", SURGERY OF (MORRIS;. clinical inference based on the fact that pancreatic disease is associated with biliary disease in from 10 to 30 per cent, of all cases, that it is more often present with long-standing dis- ease and with common duct involve- ment than with purely cholecystic inflammations. Free drainage of the pancreas is a desideratum. The peritoneum over the organ should be scarified so that gauze drainage may be brought into direct contact with the surface. A large aspirating syringe will detect collections of fluid, and these should be opened freely. Peripancreatic col- lections sometimes form in the lesser sac and point in the left loin, where they may be evacuated. Abscesses presenting anteriorly rarely adhere to the parietal peritoneum, and must be evacuated transperitoneally, some- times by a two-stage operation. Resulting sinuses are occasionally troublesome, the effects of the fer- ments evidencing themselves in the irritation of the skin. A strict anti- diabetic diet and bland ointments to the skin are helpful. The treatment of chronic pancre- atitis is that of the disease of the biliary tract found at operation. J. B. Deavtr (Boiton Mtd. and Surg. Jour.. Feb. 8, 1917;. In a series of 18 cases of acute pan- creatitis, gall-stones were found in 15. In 11 cases the gall-bladd'St; it was gelatinous in appearance. Two chromic catgut sutures were slipped around it, one at the tail, the other at the neck, and about three-fourths of it removed The drainage tube continued to drain for 43 days. The patient left the hospital on the for- tieth day, practically well. J. T. Mason (S. W. Med., xvii, 24, 1918). Calculi. — When, as occasionally happens, the pancreatic duct is ob- structed bv a calculus the condition cannot be diagnosticated readily, but is recognized when operating for some other condition, usually for gall-stones. A pancreatic calculus may sometimes be distinguished from a gall-stone with the fluoroscope. The indication is then the same as in obstruction of the common duct. One of the few surgeons who have ABDOMEN, SURGERY r^rr ,MfnM.'m 99 discussed topical pancreatic opera- tions is \'illan, but it is not easy to determine what, if any, portion of the work he describes has been done on the livings human being". For those interested we append a synopsis '■' his work. The term pancreatotomy is applied to incision of any portion of the organ or its surrounding tissues, for any purpose. If followed by suture it is termed pancreatorrhaphy. Pancrea- tostomy or fistulation of the pancreas is simply pancreatotomy with drain- age, and is a frequent procedure in the surgical treatment of cysts, abscesses, etc. Pancreatectomy, par- tial or total excision, is used chiefly in tumors of the organ (and in trau- matisms and connection). These operations will be considered else- where in detail. Pancreaticotomy, pancreaticostomy, and pancreatic an- astomoses will also be considered in detail Pancreatectomy. — This is neces- sarily partial. It has been done only to the extent of excising" tumors. The tumor must first be freed from any attachment to neig^hboring organs as well as from the pancreas itself. The excision of the tail of the pancreas is attended with much less danger. The tumors here are more likely to be pedunculated. Median laparotomy is followed by liberation of the tumor, traction and application of strong forceps or ligatures, which prevent the entr>- of blood and pancreatic juice into the peritoneal cavity. The pedicle is then divided and cut and sutured, peritoneum sutured, and wound closed. It is often prudent to tampon and drain. Excision of the head of the pancreas is difficult and dangerous. Either a part or the whole may require removal. The tumor is detached with scissors and bleeding" vessels ligated. The ducts of W'irsung and Santorini should be left intact, although the preservation of either one will suffice. If Wirsung's duct should l^e divided it is usually sutured, and the same is true of the common bile-fiuct should it be injured, although at- mospheric pressure w-ill sometimes serve to restore continuity of wound margins well enough. The operation is finished by suturing the remains of the pancreas to the duodenum. If the entire head of the pancreas is to be extirpated, it is necessary first to ligate the pancreatic duodenal artery and the right gastroepiploic, The duodenum must not be separated from the superior mesenteric artery. Wirsung's duct and the common duct must be kept intact when possible; otherwise they must be preserved b)' anastomosis. The entire pancreas can hardly be excised as a routine procedure, al- though the operation may be suc- cessfully performed on animals and even man. It is followed b)' diabetes mellitus. Pancreaticotomy. — This operation consists in incising the pancreatic duct for calculi. The duct, as m the corresponding operation on the common bile-duct, may be approached directly or indirectly through the duodenum. Simple Pancreaticotomy, — After lap- arotomy and exploration, if a cal- culus is found therein, the canal is incised, and the concrements removed b}^ forceps or other apparatus de- signed for the purpose, .Suturing of the cut duct is not necessar}\ A fistula naturally remains (pancreati- 100 ABDOMEN, SURGERY OF (MORRIS). costomy), but has a tendency to close spontaneously. Transduodenal Pancrcaticotomy. — The duodenum is lifted upward. In- cision should be made in the anterior portion, and while some surgeons advocate a transverse, others prefer a horizontal incision. The ampulla of Vater should now be located, and if a pancreatic stone is present the opening may be incised in order to extract it. Suture of the incision is not necessar}'-. Cathetering of the pancreatic duct and crushing of large calculi are recent procedures in connection with this operation. Pancreaticostomy and pancreatico- enterostomy have been done very ex- tensively in animal experiment. In human surgery, incision of the pan- creatic duct with drainage has been practised, but the operation of pan- creaticoenterostomy, which conserves the pancreatic juice in the intestine, is much more rational, and in several instances anastomoses have been ef- fected between the canal of Wirsung and some part of the digestive tract. The pancreaticoduodenal region is exposed as for pancrcaticotomy. Sutures or Murphy's button may be used. The dilated duct should be freed from adhesions and either grafted into the intestine or, what is preferable, a lateral anastomosis may be made. Pancreatic fluid coming in contact with the other tissues may cause local or distant necroses. SURGICAL AFFECTIONS OF THE SPLEEN.— Abscess.— Splenic and perisplenic abscess will in all likelihood end fatally unless some unusual path is taken by the burrow- ing pus. Incision and drainage is the tisual procedure, but, if the spleen is freely movable or readily freed from adhesions, splenectomy may be the indication of choice. Cysts. — Simple and parasitic cysts of tlie spleen are best treated by inci- sion and drainage in the same way as we treat abscesses. If tiie spleen is not bound down by adhesions, the operation may be done more safely as a two-stage procedure, the first of which consists in suturing the cyst wall to the abdominal parietes with- out opening of the former, and wait- ing for forty-eight hours for the formation of protecting adhesions. Splenomegaly. — I'^nlarged spleen from whatever cause is usually left to medical resources, unless it becomes so large as to cause serious pressure symptoms, in which case removal of the spleen may become a necessity. Floating Spleen. — While spleno- pexy has been sometimes done for this condition, most operators prefer the more radical removal of the spleen because of the difficulty of holding this organ with sutures, due to its friable tissues. The spleen may be fixed through an incision made obliquely along the left costal margin to the quadratus lumborum muscle. The patient is placed in the abdominal position upon a pad or air cushion similar to that used for forcin"- the kidneys against the abdominal wall. The peritoneal surface of the spleen is scarified, and so is the correspond- ing peritoneum of the abdominal wall. Kangaroo-tendon interrupted sutures entered at the lowest margin of the spleen serve to fasten it nearly in normal position, and a packing of gauze with a protecting apron of gutta- percha tissue gives support until supporting adhesions have formed. ABDOMEN,. SURGERY OF (MORRIS). 101 Rydygier, for fixing the spleen, makes an incision in the middle line of the abdomen high up, and forms a pocket in the parietal peritoneum through a transverse peritoneal incision, and then with the fingers forms a pouch, into which the lower half of the spleen fits. The spleen is secured in this pouch by a few points of suture. Neoplasms. — Solid tumors of all kinds and tuberculosis require early removal of the spleen. TYPICAL OPERATION OF THE SPLEEN.— Splenectomy.— The typical external incision is median in traumatic cases (not considered here), but in all others either the semilunar line or one following the costal arch at a distance of an inch or so gives better access to the pedicle. The next stage is purely exploratory and involves division of peritoneum and examination for ad- hesions. If there are no diaphrag- matic or pancreatic adhesions, it is usually possible to isolate the organ, although extensive ligation may be required. It is sometimes necessary to free the spleen from the pancreas by sacrificing a portion of the latter. The organ is then lifted out of the wound, and packed about with gauze. It must be remembered that the spleen is very easily wounded before it can be ligated ofif, and that profuse parenchymatous oozing will then delay the operation. As in other operations on abdominal viscera, traction on the pedicle may induce shock, because of the intimate con- nection with the solar plexus. The next stage consists in ligating the spleen vessels, which is accom- plished by tying oflf the splenorenal ligaments and gastrosplenic omentum and ligation of the vessels of the hilum. The latter is naturally the ideal choice, but the delay involved adds to the dangers of shock, and unless the patient is in sound condi- tion to withstand operation it may be advisable to transfix the pedicle in one or two planes according to its width, and ligate each by itself. It is well to have apparatus ready for intravenous infusion, w-hich may be begun at any moment that danger from hemorrhage appears. The after-treatment calls for no special principles. When the danger from hemorrhage or sepsis appears to be slight, the external wound may be closed at once. In malaria and leukemia the results of splenectomy have been discourag- ing. In polycythemia, Banti's dis- ease, and hemolytic jaundice, how- ever, they are more promising. T. Rovsing (Hospitalstidende, Feb. 21, 1917). After splenectomy in 2 patients, the author found a tremendous bone mar- row stimulation immediately after op- eration, as evidenced by marked leucocytosis, increased nuclear red forms, and increase in the large mononuclears and transitionals. One year later the differential count was much the same, except for the in- crease in the lymphocytes and marked increase in the nucleated red cells. There must be a more essential fac- tor in the blood cell destruction than the spleen. The spleen seems to have a very definite relation to bone mar- row cell production, and has a most definite relation to the maturing of the red cells, especially in the destruc- tive metabolism of their nuclei. In the 2 patients, who returned after a definite remission, there was much greater evidence of hemolysis than before. Gilbert (Mich. State Med. Soc. Jour., Sept., 1917). In diseases of the spleen it is abso- lutely essential that the surgeon should realize that physical findings are of minor importance, and that a 102 ABDOMEN, SURGERY OF (MORRIS). correct diagnosis must depend on the clinician who in turn must in large part rely on the various laboratory findings and special diagnostic meth- ods. The surgeon adds his opinion as to the advisability of splenectomy, based on the condition of the patient and the probable benefits from the operation. The essential features in the opera- tion as performed in the Mayo Clinic are as follows: The accessory adhe- sions and gastrosplenic omentum are separated, divided, and ligated. The dislocation of the spleen can usually be accomplished by stripping the ad- hesions with the fingers. In a few cases it is necessary to divide adhe- sions between clamps. After the spleen has been displaced a large pack may be introduced into the space formerly occupied by it. This pack serves to support the organ, and if well placed and left undisturbed, will often obviate difficult ligations of veins of some size. The spleen is now carefully elevated, and tracted toward the midline. Unless accessory vessels are encountered along the. posterior border of the pancreas, the pedicle is ligated. A very exact and safe method is first to carefully ex- pose and individualize the arterial and venous branches in the pedicle from the posterior aspect bj' dividing the fibrous investment of the pedicle. The successive division of each arterial and venous trunk beginning with the lateral vein on each side of the fan-shaped pedicle will permit a very useful mobilization of the spleen, so that the clamping of the central portion of the pedicle which usually contains the splenic artery or its largest branch, is very much favored. Usually torn veins can be ligated, but it may be necessary to leave the gauze pack in place for a few days. The difificulties of splenectomy de- pend to some extent on the condition present. In pernicious anemia it is practicalh' never attended bj' tech- nical difficulty. In hemolytic jaun- dice, it is usually without special risk, though the spleen is occasionally very large. Splenic anemia is most often associated with high operative risk, particularly in advanced stages, because of thrombotic changes in the splenic and accessory veins. The same is true in hepatic cirrhosis. In the less common diseases splenec- tomy has no special risks. In the cirrhotic and ascitic stage of splenic anemia, convalescence is protracted and uncertain. D. C. Balfour (Inter. Abst. of Surg., Jan., 1918). Splenectomy may be very difficult when the spleen is fixed to neighbor- ing organs by old, firm adhesions. Section of such adhesions occasion- ally results in fatal hemorrhage or may call for long manipulations pro- ducing shock. In such cases the writer decorticates the spleen, the plane of cleavage lying beneath the adhesions and between the thickened capsule and splenic tissue proper. By incising the capsule and inserting the fingers beneath it the spleen can be rapidly decorticated and freed. Pre- vious ligation or compression of the pedicle between clamps allows easy completion of the operation. A case is reported in which the hypertrophied spleen was removed by this method. The organ was sclerotic and adherent close to the diaphragm and the posterior abdominal wall. P. Lombard (Bull, et mem. Soc. de chir. de Par., xlvii, 826, 1921). SURGICAL DISEASES OF THE LIVER AND BILIARY PASS- AGES.— The chief occasion for sur- gical intePk'ention in these localities is gall-stone disease and its numerous consequences, for the relief of which typical operations are required. Sur- gical affections of the liver proper, while numerous, are less frequent, and for the most part are relieved by simple general procedures, as incision and drainage. Abscess of the Liver. — Here may be considered abscess of the liver proper, and suppurative pericystitis. ABDOMEN, SURGERY OF (MORRIS). 103 As soon as the diagnosis is made the pus should be drawn off with an aspirating apparatus, and most sur- geons prefer to make an explorator}' incision for this purpose. In some cases it may be necessary to excise one or more ribs and go through the pleura, in which case the operation should consist of two stages in order to allow protective adhesions to form. After the pus has been removed an incision should be made of such character as to insure complete drain- age, and the abscess cavity allowed to close. If much liver tissue has to be divided to expose the abscess cavity, it will be necessar}^ to use the cautery- for hemostasis. Subphrenic abscess may be con- sidered here, although it may occur on the left side and have no connec- tion with the liver. The general principles of operation here are the same as in abscess of the liver — ex- ploration, aspiration, and eventually incision and drainage. It may be necessarx' to go through the thoracic wall. Cysts of the Liver. — Hydatids should be extirpated if possible, the operation amounting to hepatectomy. which see. So radical a procedure is seldom carried out, and the usual inter- vention, both for hydatids and non- parasitic cysts, is incision and drain- age, v*ith the possibility of going through the thoracic wall. The oper- ation may be done in two stages with an interv^al for the formation of ad- hesions, or it may be done in a single sitting, the cyst being sutured to the operation wound before incision. In echinococcus disease of the liver, pain does not form part of the clin- ical picture, but there may be an in- flammatory reaction with adhesions which bring pain, and may even simu- late gall-stones. The pain is a warn- ing of infection. In one man of 38 years, a catarrhal jaundice and appar- ent gall-stone colics compelled an op- eration, but no gall-stones could be found. The common bile duct was enlarged but was not opened. At a later operation, it was found full of hydatid cysts and a large cj-st found in the liver was evacuated. In the differentiation from gall-stones, the shape of the enlarged liver, especially its anterior outline, is important. If the organ is not enlarged, differentia- tion may be difificult. A. Chauffard (Annales de Med., Paris, Xov.-Dec, 1917). Neoplasms. — A single focus of pri- mary cancer may sometimes be removed by hepatectomy; sarcoma is inoperable. Cirrhosis. — This has been con- sidered under Ascites (Surgery of Peritoneum). Hepatoptosis. — Hepatopexy is done usually in conjunction with other operations. The liver is scarified or brushed on the cephalad surface, and one of several methods in addition for retaining it in situ are essayed. The author includes shortening of the sus- pensory^ ligament. Cholelithiasis. — Simple accumula- tion of gall-stones, apart from the complication and secondan,- mischief, demands surgical removal. The choice then lies between cholecystos- tomy and cholecystectomy. Peterson found gall-stones in 135 out of 1066 laparotomies for pelvic disease. Kellj- found them in 14.5 per cent, and in the Mayo Clinic thej" were present in 17.1 per cent, of uterine myomata. The reasons for this large percentage of gall-stones in pelvic diseases are: (a) the high average age; (b) the high percentage of patients who have borne children; (c) the proportion of uterine and ovarian neoplasms present. He ad- vocates a routine examination for 104 ABDOMEN, SURGERY OF (MORRIS). gall-stones unless there is some con- tra-indication. When stones are re- moved, from 85 to 90 per cent of the patients will have no further trouble; otherwise 30 per cent, will suffer from further gall-bladder symptoms. His conclusion is to remove the gall- stones at the first operation when it can be done with safety. J. M. Neff (Intern. Abst. of Surg., Jan., 1919). Cholecystitis.— When the gall-blad- der has become chronically inflamed, altered by disease and adhesions, it should be extirpated. Partial chole- cystectomy is not looked upon with favor. If the process is relatively inild, with the ducts free and intact, cholecystostomy may suffice, but, like the appendix, a gall-bladder once infected is always infected. Obliteration of Bile-passages from Without. — This is most commonly due to cancer, but may be due to other tumors and inflamtriatory processes. The typical operation for obstruction from without is an anastomosis between gall-bladder and intestine (cholecystenterostomy). When this is contraindicated perma- nent drainage by a biliary fistula (cholecystostomy) is the only resort. TYPICAL OPERATIONS ON BILIARY PASSAGES AND LIVER. — These are few in number, viz., cystostomy. cystectomy, and cho- ledochotomy, cholecystenterostomy, excision of liver. Other operative procedures appear to necessitate only general principles, such as explora- tory laparotomy, evacuation of pus, etc. The typical operations on the biliary passages are performed for cholelithiasis, incidentally including chronic cholecystitis. In gall-bladder operations the writer incises the posterior sheath parallel with the tendinous fibers of the transversalis, i.e., nearly trans- versely. The level of incision is about an inch above the free end of the gall-bladder, a small opening be- ing first made for confirmation of the diagnosis with the finger. The in- cision can then be enlarged to the middle line and laterally. The trans- versalis (posterior sheath) can, with the gloved fingers, be separated from the internal oblique with ease. After the gall-bladder procedures the cut edges of the transversalis can be whipped together with catgut sutures under absolutely no tension. The support given by the uncut transver- salis renders tension stitches unnec- essary and facilitates closure of the anterior sheath and skin. McArthur (Surg., Gynec. and Obstet, Jan., 1915). Dangers of delay in operating in gall-bladder cases emphasized. The condition may be divded into 3 stages: (1) That of cholecystitis, occupying the 5 or 10 years preced- ing the operation, and which has hitherto been looked on with entirely too much indifference and compla- cence; (2) that in which stones are present but cause no complications in the ducts; (3) that of the terminal condition, e.g., empyema of the gall- bladder, gangrene, pancreatitis, etc. In the first stage the treatment indi- cated is cholecystectomy, which is followed by practically no recur- rences or secondary operations. The second stage cases should also be treated for the most part by chole- cystectomy. In the first stage the operative mortality' is less than 1 per cent., and in the second, 3 to 5 per cent. No cholecystostomies should be done in the first two stages, except in emergency cases, where the patient is in a bad condition at the time. In the older, third stage pa- tients seen 20 or 30 years from the beginning of their trouble, drainage of bile is likewise ineffectual, and cholecystostomy often does not re- sult in the removal of residual stones. W. Wayne Babcock TTrans. Amer. Med. Assoc; N. Y. Med. Jour., June 30, 1917). ABDOMEN, SURGERY OF (MORRIS). 105 Among 800 gall-bladder and other biliary cases coming under the writ- er's observation since January, 1916, 8.5 per cent. (70 cases) were secon- dary (there were also a few tertiary) operations. Of the recent series, 51 patients were originally operated by other surgeons, the remaining 19 hav- ing been operated on by the writer. In 36 of the 51, recurrence took place after a cholecystostomy, and in 15 after cholecystectomy. The longest interval between operations was 15 years. The average interval between operations in this group was about 5 years and 9 months, the average pe- riod of freedom from symptoms being about 2 years and 3 months. In his personal series it was found that in 8 cases the symptoms recurred after primary cholecystostomy, 1 af- ter choledochostomy, and 10 after cholecystectomy, or 1.3 per cent, af- ter removal and 10 per cent after drainage operation. The great vari- ance between recurrences after radi- cal surgery of the gall-bladder and those after conservative surgery shows that radical surgical treatment gives the greater prospect of a perma- nent cure. J. B. Deaver (Jour. Amer. Med. Assoc, Apr. 17, 1920). Simple Cystotomy. — The gall-blad- der, having been exposed, is incised between two toothed forceps, and the stones if present removed with finger or blunt curet, taking care to remove all possible concrements, some of which may lie close to or in the open- ing of the cystic duct. One finger should be applied along the bladder externally, to aid in localizing con- crements. Folds and diverticula resulting from cholecystitis may con- tain concrements. The cystic duct and common duct must be palpated and, if stones are contained therein, choledochotomy may be required. The author prefers amputation of the greater part of the gall-bladder as a rule, because it removes an infected structure and avoids the distress caused by the lower margin of the liver impinging upon a gall-bladder sutured to the abdominal wall. Cyst ostomy. — Cystostomy with Drainage. — This- form of cv'stostomy is really then a partial cystectomy. The tube remains in position eight or ten days, the bile escaping freely. After the tube has been withdrawn, a little bile may escape up to a week or so longer. As a rule, these fistula close spontaneously without trouble. Cholecystostomy now shows a higher mortality rate than a few years ago. This is because it is now done in extreme cases of severe gall- bladder infection with complications. Reoperations in gall-bladder dis- ease are necessitated by recurrence of stones or by the formation of ad- hesions or fistulje. Stones are much more common after cholecystostomy, but may be formed in the ducts after cholecystectomy. Adhesions of such a character as to necessitate reopera- tion because of pain or interference with the mobility of the stomach or intestines are formed usually in severe cases in which there is suppurative peritonitis and long-continued drain- age is necessary. In a given case, adhesions should not be more fre- quent or severe after removal of the gall-bladder than after drainage, pro- vided the removal is done carefully. Fistulae necessitating reoperation open from the gall-bladder or ducts into the small intestine, the colon, or the stomach. When the adhesions are very dense and extensive, gastro- enterostomy gives the best permanent relief. J. H. Branham (Amer. Jour, Obstet. and Gynec, i, 331, 1921). Cystectomy. — Surgeons have proved by experience that cystostomy had many drawbacks. It is the con- servative method, but leaves behind a diseased gall-bladder, which invites new surgical disorders. Adhesions which are invariably present cause 106 ABDOMEN, SURGERY OF (MORRIS). the organ to lose its mobility, thus increasing the liability to further in- fection. Cystectomy, an operation originally performed only on suspi- cion of cancer, has been the choice of the author for many years, the sug- gestion having come from Langen- beck's discovery^ of the safety of extirpation of the organ originally, and this idea confirmed by many operators later. Excepting in cases of cancer the autiior prefers the same operation for cystectomy that he does for cys- tostomy, for the reason that the small portion of gall-bladder which is al- lowed to remain allows of easier fastening to the drainage tube, and lessens tlie annoyance of hemorrhage from the artery and vein of the cystic duct. Cholecystectomy should be the predominant operative procedure in biliary surgery. With the destruc- tion of the lining mucosa of the gall- bladder by violent disease, the neces- sity for cholecystectomy is less evi- dent, while the mortality of the oper- ation for violent infection in the debilitated is such that a safer op- eration should be substituted; there- fore drai)i for gangrene, extirpate for catarrh. Choledocho-duodenostomy is indicated in elderly debilitated pa- tients who have or have had jaundice, or the evidence of common duct ob- struction; who will not well bear a dochotomy, who maj- have over- looked or residual stones, or who have duct obstruction, as in inoper- able carcinoma or in certain cases of mucocele, not to be treated by chole- cystectomy. It is also to be con- sidered in the treatment of Hanot's cirrhosis of the liver. The patients least able to withstand the shock of operation are those who have had prolonged external drainage of bile, jaundice, or acute septic choledo- chitis. The operative treatment should, if possible, antedate and pre- vent these complications. Excluding technical operative errors the mor- tality of biliary surgery comes largely from delayed and secondary opera- tions. W. Wayne Babcock (Can. Pract. and Rev., Aug., 1917). Gall-stone colic may be a persistent symptom even where no gall-stones can be found. Cholelithiasis should be operated upon as soon as the diagnosis is made. A diseased appen- dix, if allowed to remain, will con- tinue to distribute infection to the gall-bladder after simple drainage of the latter. As regards the relative indications for cholecystectomy and cholecysto- tomy, the author believes that tlie former should be performed under the following conditions: (1) Stones in the gall-l)ladder; (2) cholecystitis without stones; (3) gall-bladder wall disease; (4) stones or other obstruc- tions in the cystic duct; (5) adhesions around the gall-bladder which inter- fere with its pumplike action; (6) the strawberrj' or papillomatous gall- bladder; (7) malignancy. Cholecj'S- totomy should be used: (1) In pan- creatitis with jaundice; (2) in the very old and feeble cases or with poor physical condition; (3) where the operation would be dangerous be- cause of inaccessibilitj' of the gall- bladder. The appendix should be re- moved whenever there is the least suspicion that it is diseased. F. R. Benham (Annals of Surg., Oct., 1917). Technique. — The gall-bladder, hav- ing been exposed, is freed from adhe- sions and from the normal peritoneal reflection to the surface of the liver. The presence or absence of gall- stones in the bladder is only of inci- dental importance, because it is for infection of the gall-bladder that the operation is done. The freed gall- bladder can be handled very much as one would handle the appendix, and the operation from this stage on is somewhat similar. Any bile or con- cretions which are found in the lower ABDOMEN, SURGERY OF (MORRIS). 107 part of the gall-bladder or the cystic duct are stripped out with the fing-ers into the cavity of the gall-bladder proper, which remains unopened. The part which has been emptied by strip- ping with the fingers is then ligated or clamped with a pair of forceps to prevent the return of contents to the region of the operation. A longi- tudinal incision large enough to allow the entrance of a small soft- rubber catheter is then made below the clamp or ligature, and extending as far as or into the lumen of the cystic duct. The catheter is intro- duced into this opening and tied in place with a catgut suture piercing the wall of the cystic duct and cathe- ter alike. This avoids displacement caused by vomiting. The next step consists in tying another catgut suture snugly around the cystic duct or the lower portion of the gall- bladder so firmly as to cut ofif all circulation in the walls. The gall- bladder is then amputated between the clamp and ligature, and the lumen of the stump at the point of com- pression by the ligature may be steri- lized like the sturnp of the appendix, by brushing it w^ith 95 per cent, car- bolic acid neutralized a moment later with alcohol. The catheter, acting as a drainage tube, is then left escap- ing from any convenient angle of the wound of the abdominal wall. In two or three days the constricting suture is usually absorbed and the flow of bile then begins through the tube, which can be removed at any time subsequently, because the suture of catgut fastening the catheter to the cystic duct is absorbed at the same time with the constricting suture. The advantage of this tech- nique is that peritoneal adhesions have had time to wall in the area of operation so that bile or septic fluid escaping from the region of the stump makes its way safely to the surface. Sometimes it is an advantage to split the catheter longitudinally through- out its entire length, and to lay a strand of gauze loosely in the cathe- ter ;because this gives us capillary attraction to help in guiding bile or septic fluid to the surface ; and if the walls of the catheter are prevented from closing entirely, any blood or other fluid between the stump and the external incision is drawn out the same way by capillarity. Some surgeons do not consider partial excision as a typical operation. They state that cases occur in which the gall-bladder is so fragile that its liberation would be impossible, but such cases make a small part of the ones actually dealt with in practice, and. practically the same principles can be observed. Cholecystectomy without drainage advised in simple gall-bladder infec- tion, as contact of the bile with the peritoneum readily induces adhesions. The writer uses a right rectus in- cision, curving toward the xiphoid at the upper end. An incision is made into the hepatoduodenal ligament, and the pelvis of the gall-bladder grasped and pulled upward while a right angle clamp seizes the cystic duct and artery. A ligature is now placed around the cystic duct close up to its junction with the common duct, a second ligature is placed around the cystic duct and artery and the two are cut, the gall-bladder be- ing dissected out from below upward. The stump of the cystic duct is se- cured in the ligament by means of a crown suture passing through both layers of peritoneum and around the stump. The raw surface is covered with peritoneum and the abdomen closed without drainage. 108 ABDOMEN, SURGERY OF (MORRIS). Among 549 operations there were 398 cholecystostomies with a mortal- ity of 1.7 per cent., 107 cholecystec- tomies, 0.9 per cent., and 44 choledo- chotomies, 9.0 per cent. There were 26 secondary operations, 21 following cholecystostomy and 5 choledocho- tomy. A. M. Willis (Jour. Amer. Med. Assoc, Dec. 8, 1917). Of 2027 biliary operations in 2 years at the Mayo Clinic, 219 (10.8 per cent.) were secondary. Of these, 120 were for the removal of gall- bladders which had been drained pre- viously. There was only an 0.8 per cent, mortality, showing that the risk in the secondary operation is no greater than in the primary. In 109 of the 219 operations, calculi were found either in the gall-bladder, the ducts, or in both; 153 patients had cholecystitis. Adhesions were espe- cially noted in 148 cases, and in 41 there was a definite pancreatitis. Either a mucous or a biliary fistula was present in Zl cases. Seventeen of the 209 patients were definitely jaundiced. In 64 of the 219 cases both the primary and secondary op- erations had been performed in the Mayo Clinic. In 12 of these, the pri- mary operation was cholecystectomy. Judd and Harrington (Annals ot Surg., Apr., 1918). In cholecystectomy, if adequate de- pendent drainage is not established through a counterincision at the bot- tom of Morrison's pouch, then it must be ample through the abdomi- nal incision, so that by no chance will there be an accumulation of fluid at any one point which may be dis- persed by the respiratory movements. If the mucous membrane of the gall- bladder is gangrenous; if there is chronic infection of the gall-bladder; if there is a stone embedded in the cystic duct; if the wall of the cystic duct is thickened; or if the wall of the gall-bladder is thickened by scar tissue as a reaction to infection — then mere drainage of the gall-bladder will very frequentlj^ be followed by recur- rent obstruction and infection, and in these cases cholecystectomy is rec- ommended. On the other hand, if the gall-bladder has approximately nor- mal walls, and if the cystic duct is approximately normal, then no mat- ter what the size or the number of stones, if the operation is performed with due care there will be rarely if ever a postoperative pathologic cycle. In cholecystectomy the gall-bladder should be exposed by an ample in- cision so that there is free access to the base of the gall-bladder; the free- ing of tissue should be made by sharp dissection, care being taken not to injure the liver even slightly. The entire gall-bladder should be freed from its attachment so that am- ple opportunity may be given for de- termining the exact place at which the gall-bladder ends and the cystic duct begins, the division being made just proximal to this point. In death from "liver shock" follow- ing operation, the common causes are ether anesthesia, suboxidation from deep and prolonged anesthesia, trauma, and low blood-pressure. The use of a local anesthetic coupled with light gas and oxygen anesthesia; minimum trauma, secured by an am- ple incision, by sharp knife dissection, and by as brief an operation as is consistent with good surgery; blood transfusion if the blood-pressure is low, and morphine in case of pain, obviate or minimize these causes. In addition, the activity of the liver cells is increased by the application of lo- cal heat and by abundant water. To this end large hot packs should be used and adequate water equilibrium established before and after opera- tion. Crile (N. Y. State Jour, of Med., Oct., 1920). Choledochotomy. — This operation comes into play when after cystec- tomy the common duct or the hepatic duct is found diseased or containing" concrements. A wide external inci- sion is requisite when it is believed that this operation is indicated. Ex- posure may be difficult on account of the conformation of the thorax, or ABDOMEN, SURGERY OF (MORRIS). 109 when adiposity interferes. It may be necessary in such cases for an assist- ant to draw aside all the surrounding viscera widely with the hands, with g-auze beneath the fingers. If adhe- sions are absent the common duct may be lifted into the field with the fingers or a pair of padded forceps. The peritoneal covering is slit. The large vessels — hepatic arter\- and portal vein — behind the biliary pas- sages are to be avoided. A small vessel running obliquely across these must be held aside or tied and •divided. Two lymph-glands in this locality may be so enlarged and in- flamed as to simulate concrements. The common duct must now be examined for concrements and in- flammation. If concrements are pal- pable, the duct is opened between slipnooses or forceps. Bile will at once escape and must be caught up with gauze pledgets and the stones, if present, removed with small forceps or curets. As a rule, however, extensive ad- hesions are present, and the opera- tion is much more complicated. These adhesions must be separated as far as possible, and if the cystic duct has not already been opened it should be incised. If the object were not primarily to extirpate the gall- bladder, this should now be done and the cystic duct divided. The chole- dochus should next be sounded through the opening, the finger pal- pating the outside of the canal. If concrements are present, the cystic duct may be laid open slowly until the common duct is reached. By the aid of small curets and forceps, and palpation externally, small concre- ments may be extracted. If neces- sary the incision may be continued into the common duct as far as the duodenum. Extraction of stones from an inflamed or dilated chole- dochus requires the same precautions as in the case of the gall-bladder. That portion of the duct behind the duodenum is very difficult of access, unless the reflection of peritoneum from the duodenum is first cut away. In cases of this sort it has been neces- sarv^ to enter the duodenum. The conservative method is to draw the duodenum to one side after freeing the peritoneum, but this is believed by some to afifect the nutri- tion of the latter unfavorably. A drainage tube is inserted into the choledochus, and the latter sutured up to the tube by most operators, but the author usually dispenses with sutures, excepting the single one for iiolding the tube in place, because the walls of the duct normally fall together well, and atmospheric pres- sure keeps the cut margins together as well as sutures would do it, unless much unusual injury has been caused by the operative work. Writing on drainage of the com- mon duct after cholecystectomy, the author considers that such drainage by wa}^ of the stump of the cystic duct is only a temporary procedure. When prolonged drainage of the com- mon duct is needed, he opens the common duct and introduces a T- shaped rubber drainage tube. He has a number of patients wearing these tubes. This form of drainage is introduced in certain cases of pan- creatic lymphangitis, and chronic in- terstitial and interacinar pancreatitis. Early drainage of the common duct by this method or by a cholecysto- duodenostomy is the only chance for the cure of pancreatic diabetes. Deaver (Annals of Surg., Apr., 1916). In operations on the biliary pass- ages the common duct should be no ABDOMEN, SURGERY OF (MORRIS). opened: (1) When there are many small stones in the gall-bladder or the cystic duct; (2) when the com- mon duct is enlarged and its walls greatly thickened; (3) when chills, fever, and jaundice have been present before the operation. Eisendrath (Jour. Kans. Med. Soc, June, 1917). In some cases of new growth or injury, the damage to the hepatic duct may be such as to necessitate hepatico- duodenostomy. A slightly curved flap is dissected out of the duodenal wall, leaving an opening into the duodenum about 2 cm. in diameter. The flap is then approximated to the posterior and lateral aspects of the stump of the hepatic duct so as to permit muco- mucous union of the posterior half of the circumference of the duct. The remaining free margins of the opening are sutured to the liver cap- sule just above the end of the hepatic duct by continuous catgut sutures so that the opening in the duodenum not occupied by the end of the hepatic duct is effectually closed. D. C. Bal- four (Annals of Surg., Mar., 1921). Cholecystenterostomy. — A typical operation indicated is closure of the biliary passag-es from without. A long abdominal incision is required, oblique or angular, beginning at the ensiform cartilage and carried down through the right rectus muscle. The intestines are controlled by gauze. If gall-stones are present they are removed, and it must also be determined that suspected cancer of the pancreas is not a calculus in the pancreatic region. A choice of intes- tinal locality for anastomosis is then in order. The duodenum is the ideal region, but in practice a high jejunal anasto- mosis is often preferable. The gall- bladder is emptied upon gauze, and the apex seized with a clamp. A loop of jejunum is similarly held with the fingers. Both structures are opened to the extent of a finger-tip, as in gastroenterostomy, and the suture is also performed as in the latter. This locality may be fortified with omen- tum, if the operator wishes. The Murphy button is useful for this anastomosis and is used by many operators, but simple suture suffices for most cases. One must be quite sure that the cystic duct is competent be- fore attempting cholecystenteros- tomy. The gall-bladder should not be too seriously pathologic. Anas- tomosis with the colon is dangerous. Anastomosis with the duodenum above the ampulla of Vater, though more difficult than with the jejunum by the retocolic method, is ideal physiologically and is the method of choice in non-malignant conditions where a permanent stoma is consid- ered, i.e., in obstruction of the duct not removable by choledochotomy or stenosing injuries following chole- dochotomy. Anastomosis by the re- trocolic method with the jejunum should be adopted wherever anas- tomosis with the duodenum is impos- sible through adhesions or other causes, and is the method of election in all malignant conditions. By eitlier method it is essential to estab- lish a liberal stoma. All added anas- tomoses are of doubtful utility. As in cholecN'Stostomy or cholecystec- tomy, drainage of Morison's pouch is essential, with the added precaution of not allowing the drain to come in contact with the suture line. H. A. Shaw (Intern. Jour, of Surg., Aug. and Sept., 1916). Excision of Liver; Hepatectomy. — Indicated in tumors chiefly, including cysts, and sometimes after trauma- tisms. When a pedicle is present or the mass occupies the margin of the liver, hepatectomy is very easily per- formed by the aid of ligation. According to Garre, extensive resections of the liver can be carried out with the ABDOMINAL INJURIES (LAPLACE). Ill most simple means. If care is taken not to stretch the vessels in cutting through the organ and not to pull them out, it is not difificult to apply hemostatic forceps and a ligature. The vessels cut obliquely have to be taken care of by circular suture. Compression suture of the wound in the liver and catgut suture of the surface are the safest means of hemostasis. It is best to press together two wounded surfaces of the liver by suture, and, whenever possible, to make a wedge-shaped resection placed in an approximately vertical direction in rela- tion to the margin of the organ. Editors. When this is impossible the mass is removed step by step, followed by ligation of all bleeding vessels. It is often possible to ligate tliese in ad- vance of division with a needle armed with catgut. After extirpation it is in order to ligate all lumina of blood- vessels with the aid of a needle rather than with forceps, and then suture the liver with catgut. Buried sutures are undesirable for the liver, however, as blood and bile seep into them. Pressure may be brought to bear for controlling hemorrhage that is not from spouting vessels, in some cases. Pressure is obtained by carrying a long catgut ligature deeply through the wound in the liver, and fastening each end of catgut to a broad plate of sheet lead. If the entering end of catgut is first fastened to its respect- ive plate of lead, the emerging end of catgut can be tightened to any de- sirable extent before fastening it to the second lead plate. Ears fash- ioned on the lead plates can be bent over to hold the catgut ends, and silk strands fastened to the plates and led out of the wound serve for removing the plates eventually when the catgut is absorbed. More than one pair of plates may be used for an extensive liver wound. Robert T. Morris. M.D.. New York. ABDOMINAL INJURIES.- Under this heading will be considered the broad held of injuries of external origin to which the abdomen and the abdominal viscera are liable. These include contusions, which are impor- tant mainly because of the lesions to which the intra-abdominal organs are exposed ; non-penetrating wounds, in which the abdominal walls alone are injured, and penetrating ivoiinds, in which the walls and the abdominal viscera are penetrated. CONTUSION OF THE ABDO- MEN. —S Y M PT O M S .—Whether caused by blows, kicks, spent bullets, the passage of heavy bodies — such as vehicles — over the abdomen, etc., the symptoms attending a contusion in this region are not always such as to call attention to the seriousness of the lesion present. The gravest ab- dominal injuries may coexist with practically no external or general in- dication of mischief, the patient walk- ing a long distance, perhaps, without experiencing anything more than slight local pain where the blow had been received. Although the abdominal walls may be but slightly injured, the lesions may consist of extensive extravasa- tions of blood between the layers, or sufficient laceration of the muscular and other tissues to give rise to more or less local sloughing. Such lesions of the abdominal wall, however, are not always accompanied by injury of the abdominal organs. Usually, in these cases, according to Scudder, the greater the force the greater the injury, but a trivial blow may result in serious damage to intra- abdominal viscera. A hollow organ, if distended, is more vulnerable than if empty. Inquiry should be made as 112 ABDOMINAL IXJURIES (LAPLACE). to the last mealtime and as to the last micturition. The exact direction of the blow is important. The clothes of the patient sometimes offer some indication as to the injury. A trifling superficial injury of the abdominal wall may be associated with serious internal lesions, owing to the resistance offered by the ab- dominal walls and the fragility of the abdominal organs. The external ap- pearances, therefore, should not be taken as a criterion. From observations of some twenty cases of visceral injury, following contusion of the abdomen, verified by operation or autopsy by Brewer, the most prominent were pain, tender- - ness and muscular rigidity, and like- wise the most reliable. The deep- seated, localized pain following injury, especially increased by pressure, and accompanying local or general mus- cular rigidity, is one of the most constant signs of intra-abdominal injury. Brewer holds that the asso- ciation of these three symptoms is almost pathognomonic of abdominal irritation. Pain, however, is often present, with tenderness, in injuries limited to the abdominal wall ; but in these instances muscular rigidity is generally absent. In the absence of subcutaneous pain localized tender- ness with rigidity is strongly sug- gestive of visceral injur}-. Of the three symptoms, muscular rigidity is the most reliable, and sometimes the only sign. In the absence of other diseased conditions spasm of one or more of the abdominal muscles fol- lowing the traumatism may be looked upon as nature's effort to protect an injured organ from further irritation. Vomiting is a symptom often present. but not always an accompaniment of severe visceral injury. It is com- monly present with involvement of the stomach and upper part of the intestinal tube, and with injuries resulting in severe shock. The signs of free fluid in the abdominal cavity are very suggestive. In most cases, however, severe contusions of the abdominal wall, whether the deep organs are involved or not, are followed by agonizing pain in the region of the injur}', rest- lessness, nausea or vomiting, marked prostration (indicated by a small, rapid, and irregular pulse), pallor (sometimes attaining lividity), cold sweats, rigidity of the abdominal wall, meteorism, anxiety, and fear of a fatal issue. All these symptoms bear the im- print of a severe nervous commotion, and, if the extensive distribution of the sympathetic nervous system in the abdominal cavity is borne in mind, tiie fact will become evident that symptoms usually witnessed im- mediately after tlie receipt of the injur}' are due mainly to the influence of the concussion upon the sym- pathetic supply. Sudden death has been known to follow a violent blow, especially when received in the region of the solar plexus. The pain varies according to the location of the traumatism and the sensitiveness of the patient. Very severe at first, it usually becomes less marked after a few hours. It is greatly influenced by shock, profound prostration reducing its intensity by reducing sensation. Great restless- ness usually accompanies abdominal pain after injuries, as well as during other diseases, such as appendicitis, i i ABDOMINAI^ INJURIES (LAPLACE). 113 when the suffering is due to a local- return to the normal line after having ized trouble. The pain may be gone beyond or below it. The usual radiated in various directions, — the belief that a subnormal temperature shoulder, the umbilicus, the left always follows internal hemorrhage axilla, the testicles, etc. — according is fallacious ; for it may also be raised, to the site of the primary lesion. The temperature, therefore, is of no Local tenderness is usually marked value as a guide, over the site of the traumatism. Hematemesis may assist in estab- Th( vomitmg varies greatly m Hshinsf the diagrnosis of lesion in the intensity from mere nausea to the stomach or the upper portion of the most violent expulsive efforts, which intestinal tract, while the presence of are liable, by the strain upon the abdominal organs, to suddenly in- crease the extent of the lesions. The vomited matter sometimes contains blood, especially if the upper portion of the digestive tract is involved in blood in the stools may do the same as regards lesions of the intestines as a wliole. including the colon. But, in itself, this symptom is, by no means, characteristic, since a violent strain may cause sudden engorge- the injury. Constant and persistent ment of pharyngeal, gastric, rectal, vomiting tends to indicate a contu- or hemorrhoidal vessels and then, sion accompanied by visceral lesions, several days after the accident, blood- According to Berndt, in simple cases the vomiting is repeated but two or three times. When the intestine is ruptured the vomiting is persistent and intractable and liver-dullness is absent. rupture ensue. Even when present, streaks in vomited matter or stools are not always indicative of an alarm- ing condition. Blood in the urine is a more reliable sign of lesion in the urinary tract. The degree of shock depends upon especially the kidney and bladder. the nature and extent of the injury Anuria is also indicative of lesions in and especially upon the amount of these organs ; but, as shock frequently blood lost. When the signs of col- arrests the flow of urine, it is only lapse gradually betome more marked, valuable as a symptom after all symp- internal hemorrhage from rupture of toms of shock have passed, one or more of the viscera is to be Hemorrhage into the orbits and feared. from the ears are occasionally met The pulse, usually rapid and weak with when the concussion has been at first, gradually becomes stronger and slower if a favorable reaction is about to take place. If, on the con- trary, an unfavorable course is being very severe. This symptom does not necessarily indicate that the injury is an unusually dangerous one. A few hours after the accident the taken and some complication is to pain usually becomes reduced; the occur, its rapidity and tension may patient may be more quiet and, per- become increased. Irregularity is haps, somnolent, although the pulse not a favorable indication if it per- remains in its former condition. This sists. Temperature is independent of period lasts between twelve and the pulse, except when a favorable twenty-four hours. If at the end of reaction is taking place, when it may this time there be no complication, 1—8 114 ABDOMINAL INJURIES (LAPLACE). a visceral lesion is probably not present. If, on the contrary, the symptoms gradually increase in in- tensity, the likelihood of grave injury is very great. In the light of present knowledge, however, the practitioner should not delay active procedures until the patient's life becomes compromised by permitting the mechanical injury produced to start an infectious proc- ess, when the manner in which the injury was inflicted and the force ap- plied tend to suggest serious internal lesion. An exploratory incision is sometimes permissible (see colored plate). DIAGNOSIS. — In abdominal con- tusions the diagnosis should primarily be based upon the history of the acci- dent, the manner in which the injury occurred, the shape of the body, or bodies, by means of which the trau- matism was inflicted, and the degree of percussive force applied, and, secondarily, upon the symptoms present. The value of abdominal or bimanual vaginal examination of patients while in a hot bath has been emphasized by Carter. In many instances the abdominal relaxa- tion obtained is quite equal to that ob- tained under an anesthetic, with the added advantage that the patient can help the examiner by voluntary movements, such as deep inspiration, holding the breath, etc. Report of 2 cases of injury fol- lowed by a quiescent period. At oper- ation, the small intestine was found completelj' severed and the ends ot the intestine closed off by the local reflexes so that there was no leakage. After certain injuries to the abdomen there is frequently such a period of from 12 to 24 hours during which the surgeon and patient may decide what is to be done. Purgatives prove harm- ful. G. E. Armstrong (Jour. Amer. Med. Assoc, Dec. 6, 1919). Lesions of the Intestinal Tract. — Various theories have been advanced as to the manner in which rupture of the intestine is brought about, but experiments have shown that squeez- ing of the gut betw^een the com- pressed abdominal wall and the verte- bral column is the main mechanical factor brought into action. In reporting a personal case of re- troperitoneal rupture of the duodenum in which the points of interest were slight general and local reaction from the resulting al)sccss, due to the rela- tive sterility of the duodenal con- tents, and also a point of tenderness beneath the twelfth rib, the writer reviews a series of 22 cases. The in- jury is peculiar to the active working male, and is always due to trauma. In the 22 cases, 82 per cent, were situated in the second or third portions of the duodenum, and 15 showed retroperitoneal extravasations at operation. This is always found either in the root of the transverse mesocolon, in the root of the mesen- tery of the small bowel, or involving, in addition, the intervening retroperi- toneal space, and is usually of rapid formation. The contents is a bloody, bile-stained fluid mixed with gas that soon becomes purulent. The peri- toneal cavity is clean or at best con- tains a very small amount of free blood-stained fluid, probably from a minute injury to some viscus. Peri- tonitis is undoubtedly delayed for some time by the intact peritoneum, but ultimately occurs. There may ap- pear a fixed tumor in the upper right quadrant, but this was only noted in 2 cases. Of the 22 cases, 20 were op- erated on and but 3 recovered. No case survived when operation was postponed longer than 24 hours. R. T. Miller (Annals of Surg., Ixiv, .S50, 1916). Injury to the bowel by direct vio- lence to the abdominal wall is pos- sible under the following conditions: First, when the force is sufficient to carry the abdominal wall back so ABDOMINAL INJURIES (LAPLACE). 115 that the bowel is caught between the object producing the force and the body of a lumbar vertel)ra. The posi- tion of the patient at the time of in- jury with the body inclined forward and a weak, flabby abdominal wall would predispose to this form of injury. A second possible condition in which rupture of the bowel might occur is when it is filled by a solid or semi-solid matter that offers suffi- cient resistance to rupture the gut before it can recede from the oncom- ing object producing the sudden blow. A third possible condition is that rupture may occur by reflex stimulation of the intestinal nerves through the nerve supply of the ab- dominal wall. Rigidity of the abdominal muscles, pain of a severe type, a strained and anxious countenance, a varying de- gree of shock, and a rapidly increas- ing pulse-rate are sufficient signs to lead to a diagnosis and to indicate immediate operation. J. S. Wright (Can. Med. Assoc. Jour., viii, 228, 1918). Crushing' against the ileum is rarely produced. Another, although rare, cause of rupture is the presence, in the intestinal tract, of liquid or semi- liquid material, the sudden circum- scribed pressure exerted upon the gut causing it to burst" through overdis- tention. The small intestine is the seat of lesion in 75 per cent, of the cases of rupture in the course of the intestinal canal. Hence the impor- tance of carefully ascertaining in each case the direction from which the percussive force came, the inten- sity of that force, and the relative position of the organs between the site of pressure and the spinal column. Another factor of importance in es- tablishing a diagnosis is the size of the instrument causing the injury. Lesions of the digestive canal, for instance, are usually the result of violent and sudden percussion pro- duced by a body over a limited sur- face of the abdominal wall. The predisposing factors are the presence of solid, semisolid, or fluid matter in the hollow viscera; lean- ness of the individual, and intestinal adhesions. Any of the above accidental causes of injury being fulfilled, rupture of some portion of the gastrointestinal tract is likely, especially if there is loss of consciousness at the time of the accident, followed by collapse, severe pain, a rapid and weak pulse, vomiting, tympanites due to the escape of intestinal gas into the ab- dominal cavity, and tenderness and rigidity of the abdoininal walls. Frankel has laid great stress on the slow rise of the temperature froin hour to hour. A pulse above 100, if hemorrhage can be excluded, speaks in favor of rupture of the intestines and incipient peritonitis. Case of rupture of the jejunum in a boy who was struck in the abdomen while playing football. The main symptoms were vomiting, elevation of temperature to 101° F. (38.3° C), pulse 118 within a few hours after the accident, some rigidity of the upper abdomen, but marked absence of shock and severe pain. Twenty-eight hours after injury the pulse was 112; the temperature, 100.5° F. (38° C), the leucocytes, 25,000. Vomiting had occurred 5 times, the last vomitus having a fecal odor. The bowels had acted once; there was slight tympa- nites. Operation revealed a large rent in jejunum. Suture with drain- age of the abdominal cavity was fol- lowed by recovery. Leakage from the jejunum is less dangerous than from the ileum, where bacteria are present in greater numbers. F. K. Boland (Jour. Med. Assoc, of Ga., vii, 74, 1917). 116 ABDOMINAL INJURIES (LAPLACE). Such a diagnosis is further strength- ened by hematemesis or bloody stools, the former tending to indicate a lesion of the stomach. Death occurs in 96 per cent, of such cases if un- operated. In the differential diagnosis of ab- dominal contusion the greatest feat- ure for an early recognition of the existing conditions is whether there is unilateral or general tension of the abdominal wall, unless there is con- siderable blood-suffusion at the in- jured place. Aside from the reflex tension of the abdominal muscles, a sliglit, but distinct exacerbation of the general condition during the first few hours following the injury is a point of importance. With very care- ful observation, three or four hours may be allowed to elapse, l)ut even then there is the possibility of error. Koerte reported a case where he was absolutely certain of his diagnosis and had decided to operate; the pa- tient, however, refused operation and made a smooth recovery. In the most favorable cases, where is but a slight tear, the mucous mem- brane will prolapse and occlude the aperture. Neighboring loops or the omentum will form a laj^er over the lesion with agglutination or adhesion, so that recover}^ may take place. If there is exudation of intestinal con- tents, a circumscribed, encysted ab- scess may form which is capable of resorption, or secondary perforation into the intestine or outward may occur; but it is equally possible that pus will find the dangerous route into the free abdominal cavity. In the most unfavorable cases, there is neither occlusion nor abscess for- mation; the inflammation will rapidly spread over large areas or over the entire peritoneum and cannot be checked. As earlj' as four hours, ex- udate may be found; likewise, fibrin- ous deposits on the various loops. The more or less fulminating course is not only dependent upon the quan- tity of the exudate, but also on its infectious nature. Statistics show the rarity of cases in which the most favorable course, as depicted above, takes place. Of 160 cases of subcutaneous intestinal rupture in which the expectant treat- ment was instituted, 149 died: of the 11 which recovered, 10 had to be operated during treatment for fecal abscesses and fistula?. Enderlen (Post-Graduate, July, 1911). For the detection of intraperitoneal rupture of the intestine from con- tusion, the abdomen should be care- fully examined every hour for pain, intensification of existing pain, and local tenderness. When the indica- tions point to rupture, expectancy should be limited to 1 hour. The writer sutures the rupture or resects the intestine and then mops up the peritoneal cavity without washing it out. He has had 8 complete re- coveries and 3 deaths. Soederlund (Nordisktmed. Arkiv, li, No. 5, 1919). Reports of 30 cases of detachment of the mesentery in abdominal con- tusion have been found by the writer. In 8 of these the detachment was the only lesion. It usually occurs in the terminal part of the ileum, but in 4 cases it was in the middle part, and in 3 in the first part. The symptoms may be those of interna] hemorrhage and acute anemia. Or there may be an acute peritoneal syndrome. In a third type there is a syndrome of simple parietal contusion. In the first 2 types the symptoms demand immediate laparotomy. In the third there is no symptom of internal hemorrhage or peritonitis and the surgeon will probably delay lapar- otomy. In the author's case absence of sj-mptoms continued for 36 hours. In such cases gangrene of the de- tached intestine is certain to develop unless a prompt operation is per- formed. The peritonitis becomes manifest only 24 to 40 hours after the injury. L. Sencert (Bull, et mem. Soc. de chir. de Paris, xlvii, 758, 1921). Lesions of the Stomach, — Blows seldom cause rupture of the stomach, the elasticity of the organ, even when ABDOMINAL L\7URIES (LAPLACE). 117 containing liquid or semiliquid ma- terial, being such as to cause it to escape injury under sudden impact or great pressure. It is also pro- tected by the lower ribs, the liver, and the intestines. Nevertheless, this orgfan is occasionallv involved in traumatism afifecting other abdom- inal viscera. In the majority of cases the rent is found near the pyloric orihce. but the greater curvature ma^^ be the seat of the lesion, while the entire organ is occasionally torn from end to end. In the latter case, however, death ensues almost imme- diately in practically all cases. Pres- sure during lavage of the stomach may also cause laceration of the mucous membrane. In the case of incomplete tears there may be hematemesis and severe localized pain resembling that of gas- tric ulcer, — gnawing and burning in character. This is followed by local- ized inflammation with tendency to the formation of adhesions. Hemor- rhage between the coats of the stom- ach may also occur in incomplete tears, a cyst-like pocket being formed. Violent pressure upon the stomach may cause it to be crushed against the spinal column, and the mucous surface be lacerated by interpressure of the anterior and posterior walls of the organ. In such a case a marked lesion necessarily follows, giving rise to copious hematemesis. Rupture of the stomach implicates the peritoneal coat in the majority of cases, the elasticity of the peritoneal investment being less than that of the two internal coats : muscular and mucous. The contents of the stom- ach, or a portion of them, escape into the peritoneal cavity and cause severe suffering and shock, followed promptly by death or septic peritoni- tis. Brsant teaches that a ruptured intestine is probably present, though, this is not certain, when, after a diffuse injury to the abdomen or a severe local injury as the immediate result of the accident, there is little collapse, and when vomiting soon be- comes a prominent and persistent symptom, with lasting local pain and great thirst, with or without abdom- inal enlargement. According to Gluzinski, two signs which enable the physician to diag- nose the occurrence of intestinal per- foration before peritonitis has had time to manifest itself: 1, distinct- ness of the murmurs of the heart and respiration during auscultation of the abdomen, due to the presence of in- testinal gases in the peritoneal cavity. 2, change in the pulse, which, at the moment of perforation, becomes accel- erated, to slacken some hours later, owing to the absorption of putrid gases acting as cardiac poison. In every case of perforation of the stomach or duodenum, free gas and fluid are present in the peritonea! cavity. The gas inay pass between the liver and diaphragm, as shown by the X-ray, and cause obliteration of liver dullness. Much dependence can- not be placed on liver percussion as ordinarily practised, because of the very great variations, both in health and disease. Change of the patient's position, however, will cause the fluid to flow to the dependent part, and the air to rise to the top, thus intensify- ing the findings. There is tympany over a wide liver area and again flat- ness over the same area on change of position. Normally there is also a change in the liver percussion note on change of posture, and normal liver changes must be recognized be- fore positive deductions are made. A fair comparison is the difference de- tected in shifting flank dullness in 118 ABDOMINAL IN7URIES (LAPLACE). moderate ascites and in the normal abdomen. M. T. Field (Boston Med. and Surg. Jour., Feb. 14, 1918). Lesions of the Liver. — The liver, owing to its friable nature, its size, and its anatomical position, is the organ most frequently injured, be- cause indirect concussion may cause a profound lesion. A fall from a great height into water may thus cause a gaping rent of the capsule and parenchyma and open a large number of vessels. Severe and sud- den blows of any kind, especially those involving much surface, over the abdominal wall may thus cause injur>^ to this organ. Again, its soft- ness, which may be increased by hypertrophy, causes it to yield readily to the crushing produced by carriage- wheels, car-bumpers, etc. Rupture of the liver according to Battle, is an extremely fatal accident, and the symptoms v/hich ensue are usually marked and serious. Shock is present, frequently passing into collapse and death. Short of this there are vomiting, rapid pulse and respiration, pallor, etc. In this accident rigidity of the abdominal wall is very evi- dent, so that it may appear boardlike. Tenderness becomes localized to the hepatic region, and there is shifting dull- ness in the flanks with the ordinary symp- toms of loss of blood, according to the amount of it which is effused; the man becoming restless with a rapid, weak pulse, sighing respiration, and what is called "air hunger." Jaundice may be a late symptom and is therefore of no use in the early diagnosis which is so very important. The severity of all the general symptoms is usually increased. The pain, when the liver is seriously in- jured, is peculiar; it radiates from the right hypochondrium to the waist, the scrobiculus cordis, or the scapular region. The respiration is generally embarrassed ; there is marked shock. Examination of the feces may show the absence of bile, especially if the bile-duct is ruptured : an occasional complication. The dissemination of bile in the system causes itching and, after a time, jaundice. The escape of bile into the peritoneal cavity may not give rise to peritonitis, however, this fluid being aseptic. A serous exudate may result from the irrita- tion caused by its presence, forming a composite fluid which may be re- tained in the peritoneal cavity a con- siderable time. The most reliable symptoin is the defense musculaire emphasized by liartmann and Trendelenburg. Rig- idity is not the proper term for this condition, for rigidity rather denotes a tetanic state of the abdominal mus- cles, whether stimulated by pressure of the hand or not. It is not marked, except in the gravest cases, shortly after injury, but develops in the fol- lowing few hours from irritation of the peritoneum by the hemorrhage of intestinal contents from rupture of the intestines. It was especially mentioned twenty-four times in the 44 cases, and in the remainder other signs, notably those of internal hemorrhage, were so marked that it was not noted in the history. Never- theless, it is not an infallible symp- tom, as proved by 2 cases related by Baum. Riebel (Quarterly Bull. N. W. Univ. Med. School, Sept., 1910). In reporting 3 cases of laceration of the right coronary ligament of the liver due to blows in the costal area on the right side, the writer gives the following diagnostic differential signs: From a renal injury, by the absence of costovertebral tenderness, absence of blood in the urine; the pain is located by the patient more anter- iorly in the flank and higher up than in renal injury. There are also signs of intraperitoneal irritation. From a rupture of the liver bulk it differs only in degree; the symptoms are more active, collapse is added to ABDOMINAL IN7URIES (LAPLACE). 119 the shock, the abdomen is held more rigid, breathing is entirely costal, and the pulse continues to fail. M. R. Bookman (Med. Rec, Jan. 13, 1917). Umbilical ecchymosis is regarded as a symptom of wounds of the liver by the writer. His case was one of thoraco-abdominal injury, associated with wounds of the lung and the convex surface of the liver, in which ecchymosis in the upper half of the umbilicus appeared. Bonnet (Lyon Chir., Sept.-Oct, 1919). A rent is probable after a severe injury- if there is collapse, if the pulse becomes more rapid and small, if the patient shows signs of exsanguinity. if the area of liver-dullness on per- cussion is increased, and if pain radiating- to the scapular region is complained of. Severe injury may exist, hovv^ever, without these indica- tions. Lesions of the Gall-bladder or Biliary Ducts. — Blows and other con- ditions capable of catising hepatic rents sometimes implicate these organs in the lesion. There may be severe pain in the right hypochon- drium if a rupture exists, vomiting of food and bile, and icterus. The urine is usually dark-mahogany and the stools ash-gray in color. Tender- ness over the hepatic region is usually marked. The intensity of the symp- toms depend to a degree upon the quantity of bile voided into the abdominal cavity; but, this secretion being aseptic, peritonitis only occurs as a complication when the perito- neum is itself implicated in the trau- matism, or when the lesion is at the junction of the biliar\' tract and the intestinal canal, the latter in that case acting as a source of infection. In the diagnosis of injury of the liver bradycardia is a suggestive sign. In one case the liver had been rup- tured by the kick of a horse and the pulse was only 48. In the other case the liver had been sutured and the pulse was 52. Several writers have mentioned bradycardia with injur}- of the liver, and ascribe diagnostic importance to it. The writer experi- mented on animals to deterinine the influence on the pulse of injury or liver and spleen. The results with 20 animals showed that bradycardia is a characteristic symptom of injury of the liver, but that its absence does not exclude injury of this organ. Finsterer (Archiv f. klin. Chir., Bd. xcv, Nu. 2, 1911). According to Tilton hepatic injuries usually cause pain to radiate to the right shoulder. Inasmuch as there is also local pain on respiration, the chest does move as much on the right as on the left. This may lead to a misconstruction of the diag- nosis, for it suggests to the casual ob- server thoracic injury. The blood gravi- tates into the right iliac fossa and may give well-marked dullness. Disappearance of liver dullness is due to beginning tj'm- panites and is therefore not of great diag- nostic importance. Jaundice is occasion- ally present, but usually does not appear until the second or fourth day. Ludwig found it 24 times in 267 cases. Its pres- ence usually signifies injuries of the bile- duct. Lesions of the Spleen. — The catises of injury to this organ are the same as those of the liver. Rents, san- guineous infiltration, and partial crushing are the lesions most fre- quently observed. Enlargement of spleen through a malarial cachexia renders it susceptible to lesions which traumatism would not give rise to were it in its normal state. The malarial spleen seems particu- larly susceptible to rupture. The presence of a slow and strong pulse, after the phase of shock has passed oft', does not exclude the possibility of a ruptured liver, since it is due to absorption of the biliary acids. Ab- dominal rigidity, the presence of an 120 ABDOMINAL INJURIES (LAPLACE). intra-abdominal fluid collection, local- ized or radiating pain, are the main symptoms. H. Finsterer (Wiener med. Woch., July 6, 1918). In extensive lesions copious hemor- rhage usually takes place and death rapidly follows. If the lesion present is less severe, however, and the hemor- rhage be moderate, there is tendency to collapse, increasing pallor, and a feeling of suffocation. The latter symptom and severe radiating pain in the region of the spleen are gener- ally present, besides the signs pecul- iar to all abdominal injuries. If the patient survives sufficiently long the immediate effects of the traumatism, peritonitis or abscess and other com- plications frequently result. Severe local pain generally continues for some time, and chills are not infre- quent. Percussion shows the organ to be more or less enlarged. According to Trendelenburg, vomit- ing is a most important guide in the diagnosis of rupture of the spleen; in simple contusion of the alimentary, tract it is very seldom if ever encountered. The symptoms of traumatic rupture of the spleen are essentially those of internal hemorrhage, and the diagno- sis is usually not made until after ab- dominal section. The symptoms are obscure so far as enabling the distinc- tion whether the spleen or some other abdominal viscus is ruptured. However, there should be no difficulty in diagnosticating the existence of hemorrhage into the abdominal cav- ity, and, when this condition is recog- nized, abdominal section is indicated. The incision should be made over the region of greatest dullness, if this can be determined. If percussion elicits a note of higher pitch in one flank than in the other, a valuable hint as to the source of hemorrhage has been obtained. Should the hemorrhage be sufficiently severe to give a percus- sion note of equal dullness in all regions the indication is to make the incision in the middle line. The treat- ment is essentially surgical, the ob- ject being the control oi hemorrhage, and all authorities are agreed that this end is most certainly accom- plished by splenectomy. The mortal- ity following removal of the healthy spleen for rupture is al>out 40 per cent., whereas that of non-operative treatment is probably 100 per cent. Watkins (Med. Rec, Mar. 14, 1908). Case of a man who fell over an ob- struction, got up and walked a few steps, but was then seized with pains in the left thoracic base region. On examination his pulse was only slightly weakened. Beneath the left costal border there was some degree of muscular resistance. The pains con- tinued and became more violent. Later his appearance grew worse and the abdomen became rigid. A diag- nosis of intraperitoneal hemorrhage probably due to rupture of the spleen was made, and the patient operated upon. The abdomen was full of blood and the spleen separated into 2 distinct parts by a rupture perpen- dicular to its major axis. The pedicle was ligatured and the splenic cavity cleaned out. The postoperative course was simple. Examination showed that the rupture was at the union of the anterior and middle thirds; the capsule was largely de- nuded for about 3 cm. The author believes the rupture occurred in two stages: First, a parenchymal rupture with intrasplenic hemorrhage and for- mation of a subcapsular hematoma; secondly, upon an effort, capsular rupture and peritoneal inundation. Lefevre (Presse Med., p. 617, 1917). Lesions of the Kidneys. — The kidney is firmly held in place by its attachments, while its consistence is such as to preclude elasticity. Hence, a blow or undue pressure may cause rupture. All the causes of injur} that may take part in the production of lesions elsewhere may also induce i i ABDOMINAL LXJURIES (LAPLACE). 121 renal lesions, which may consist of contusion, rupture, or laceration. The 2 salient symptoms in con- tused wounds of the kidney in war are hematuria and perirenal hemat- oma. The first is observed in 95 per cent, of the cases. Unless primary hematuria is abundant, expectant treatment may be observed. Hematoma is of equal value v^^ith hematuria as a symptom. If it con- stantly increases, it indicates imme- diate operation which may otherwise be deferred. There is. however, dan- ger of the hematoma becoming in- fected if no operation is done, and there is a second danger of fibrous coating being formed around the kid- ney which may prevent its function- ing and giving rise to a chronic sclerous perinephritis. P. Xogues (Jour. d'Urol., vii, 123, 1918). The hidden gravity of such cases is well shown by the case of a girl, 4 years old, who fell over backward while on a hobln- horse, the saddle striking her directly across the ab- domen at the umbilical level. The onl}' immediate effect was slight pain and tenderness over the right lower ribs. On the second day the tem- perature rose to 103.5° F. (39.7° C). The tentative diagnosis was either injury of an abnormally placed ap- pendix or a hematoma of the ab- dominal wall. Although the acute symptoms then subsided, a mass ap- peared 1 week later below the free border of the ribs on the right side. This mass was very tender and pain- ful and was thought to be the liver, either abscessed or containing a new- growth, or an encapsulated hema- toma. It rapidly increased in size, and there was cardiac and respira- tory oppression with progressive anemia. On the 36th day an explora- tory laparotomy was done. The liver was found to be normal but entirely displaced by a large mass, which when opened was found to contain serum, blood and clots, and a few soft pale-gray masses resembling sar- comatous tissue of the small round- celled type. This mass proved to be the right kidney entirely disorganized and broken down, the tumor wall being the kidney capsule. The kid- ney was drained and packed. Autopsy revealed a slight loss of cortical substance and contusion of the kidnej' capsule, allowing a slow but progressive hemorrhage to take place beneath and within the capsule. H. P. DeForest (Jour. Dis. of Chil- dren, XV, 273, 1918). Besides the symptoms common to severe abdominal traumatism there may be increased pain in the lumbar region with radiations in the direc- tion of the pubis and rigidity of the muscles. Dullness on percussion is sometimes elicited. Anuria may also occur, but this is not a characteristic sign. Hematuria is an important in- dication of renal laceration, however, although it may not present itself at once ; it may be followed by the ap- pearance of pus. The catheter should be used in these. Retraction of the testicles is also said to occur (Rayer). The ureter is verv' rarely involved ; when it is, the symptoms are not modified. Enlargement of the lumbar and hypochondriac regions is present in the majority of severe cases, but may supervene late in the history of the case. Thanks to the compensatory work of the uninjured kidney, the mortality of renal lesions is not so marked as when other abdominal organs are injured. Even severe wounds have been known to heal. If large renal vessels are torn, marked Hvidity occurs, the patient rapidly becoming exsanguine. Death may thus follow ver\- soon. Involvement of the peritoneum in the injury is promptly followed by peritonitis, the signs of this afifection appearing a few hours after the 122 ABDOMINAL IN'JURIES (LAPLACE). receipt of the injury. Sepsis is not an infrequent complication in un- operated cases. When a patient has sustained an abdominal injurj% manifesting the usual symptoms of shock, a gradually increasing resistant swelling over the kidney region requires prompt surg- ical intervention. The operation sliould be performed within the first 12 hours after injury. The surgeon can discriminate between mild cases which need no surgical interference and those that manifest injury to the deep-seated organs. C. W. Roberts (Jour. Med. Assoc. Ga., vii, 81, 1917), PROGNOSIS.— Death almost in- variably attended rupture of the in- testinal tract prior to the introduc- tion of exploratory abdominal sec- tion, and prompt resort to active surg-ical procedures, when necessary, is indicated. As to the liver, as late as 1864 wounds of this organ were considered as practically hopeless in even*' in- stance. While a very small propor- tion of these cases recover without surgical interference, as is shown by the scars occasionally found in the hepatic parenchyma, the fact remains that an exploratory laparotomy, per- mitting the surgeon quickly to arrest the loss of blood in case of hemor- rhage and to rid the peritoneal cavity of accumulated extraneous fluids, has greatly reduced the mortality. The prognosis becomes much more un- favorable when peritonitis has set in, but a fatal issue ma}'- sometimes be averted, even in advanced cases of this complication, by surgical inter- vention. The same remarks apply to rupture of the gall-bladder. Slight contusions of spleen heal readily, but rents and tears of any importance are frequently followed by fatal hemorrhage. Abscesses oc- casionally complicate convalescence. The great majority of cases of rupture of the kidney that recover are those in which the initial lesion had been comparatively slight. In the graver cases, in which there is copious hemorrhage into the peri- nephric tissues or into the peritoneal cavity, of which the growing exsan- guinity of the patient is an indication, the prognosis depends upon the speed with which adequate surgical procedures are instituted. Occasion- ally, however, the blood is held in check by the renal capsule. The prognosis depends greatly, therefore, upon the patient's ability to stand operative procedures suitable to establish a positive diagnosis and bring tlie lesion that may at any moment destroy life within the imme- diate reach of art's highest powers. \\'hen serious injury is rendered prob- able by the nature of the accident, and the symptoms present also indi- cate a serious lesion, an exploratory incision, if the patient is not past relief, a careful examination of the organs involved, arrest of hemor- rhage, closure of the disrupted tis- sues, or cleansing of the abdominal cavity may save him even when his condition appears almost hopeless. Again, the prognosis is influenced by the time elapsing between the accident and the institution of surgi- cal procedures. The sooner they are resorted to, all tilings considered, the greater the chances of success. No case can be considered as hope- less unless a subnormal temperature, cold and cyanosed extremities, and other signs indicate that the end is near. Even when performed late in the ABDOMINAL INJURIES (LAPLACE). 123 history of the case, adequate operat- ive measures sometimes prove suc- cessful. The mortalit}^ in injuries of the kidney is, under the best surgical procedures, about 30 per cent., according to Crawford. Death in these cases, if not immediate, as the result of shock, or hemorrhage, or in- jury to other important organs, is due (1) to-anuria, (2) to infection, or (3) to secon- dary hemorrhage. Anuria is probably due to a reflex contraction of vessels in the sound kidney owing to stimulation of the splanchnics and the vagus endings (Mas- ius). Secondarj^ hemorrhage may not oc- cur for a week or ten days after injury and is then due to a disintegration of biood-clots, which are acted upon by the urine. Infection may be (a) local, with deep cellulitis and subsequent general in- volvement; (b) peritonitis, or (c) an as- cending involvement of the opposite kid- ney due to the breaking down of blood- clots in the bladder. The early recognition of a rupture of the bladder g'reatly influences the prognosis. About 60 per cent, of the most unpromising lesion, intraperi- toneal laceration, are saved by prompt surgical measures. The remaining 40 per cent, are unsuccessful mainly on account of delay in resorting to abdominal section. A favorable re- sult has, nevertheless, followed lap- arotomy as much as fifty-four hours after the rupture. TREATMENT. — Shock. — Shock or collapse, though unreliable as a sign of severe injury to the abdom- inal viscera, is, nevertheless, an alarming condition, especially if the temperature is subnormal and the breath is shallow, and it should at once receive attention. The patient is placed in bed with the head low, and a free supply of pure air insured, supplemented with oxygen if prac- ticable. Hot-water bottles are placed around him and he is covered with blankets previously warmed, if pos- sible, or wrung out of hot water. Two main elements have to be borne in mind in this class of cases: (1) that the state of shock is due to a direct commotion of the sympa- thetic system with probable inhibition of the heart's action, and (2) the pos- sibility of an internal lesion which may involve death by exsanguination or the outpour into the peritoneal cavity of gastric or intestinal fluids. While the first condition calls for stimulants adapted to sustain the flag- ging heart and restore the action of the vasomotors, the agents employed should not be administered by the mouth, since, in case of rupture of the stomach, the duodenum, or jeju- num, a portion, at least, of the fluid may be added to those that may have found their way into the peritoneal cavity. Rectal and subcutaneous in- jections should be resorted to. If no remedy be at hand, subcuta- neous injections of 1 dram of whisky or brandy may be employed, and re- peated ever}' five or six minutes until reaction occurs. A turpentine stupe or a fresh mustard poultice (not plaster) over the xiphoid cartilage, and a rectal injection composed of a tablespoonful of turpentine, a raw egg, and a teacupful of warm water, sometimes act with surprising rapid- ity. Hypodermic injections of ether, or, better still, tincture of digitalis with %2o grain of atropine, repeated in fifteen minutes, are necessary' to sustain cardiac action. After the second dose the digitalis may be in- jected alone several times more. These measures are greatly assisted by galvanic stimulation of the phrenic nerve, the negative pole, moistened in a solution of chloride of ammonium. 124 ABDOMINAL INJURIES (LAPLACE). being applied to the neck in the de- pression immediately in front of the sternomastoid muscle, and the posi- tive over the epigastrium. These means are sometimes ineffi- cient and hypodermoclysis should be performed. If a fatal issue seems inevitable, saline transfusion is indi- cated. Cases of abdominal wounds in more or less marked shock should receive at once a subcutaneous injection of 1 or 2 eg. (Mi to \'3 grain) of mor- phine, and then means be applied to increase the blood-pressure and vital- ity. Camphorated oil is given after the morphine in doses varying from 3 to 4 c.c. (48 to 64 minims), at most 2 c.c. (32 minims) being injected at the same point. Adrenalin is likewise given subcutaneously in doses of 1 or 2 c.c. (16 to 32 minims) of a 1:1000 solution. The saline may be administered hypodermically or intra- venously. If the shock is very severe, the patient should rest for not over two hours, the stimulant being re- peated at intervals. During the opera- tion it is necessary to combat shock by repeating injections at intervals. Postoperatively the Fowler position is not indicated in all cases; some may require a lateral decubitus or even a horizontal position with the head pendent, especially when there has been abundant hemorrhage and threatening anemia. Food and all drink is forbidden for the first twelve hours. Then only a spoonful of milk and water, brandy, or wine with water is given every hour. To over- come meteorism enemas of equal parts of warm water and glycerine are personally administered by the phy- sician. After expulsion of gas, the intestine is cleansed with warm salt water. W. Stoppato (Poficlin., xxiv, sez. chir., 1917). With reference to abdominal wounds in civil life, stress is laid on the increasing frequency with which preventable fatalities are observed from injury to intra-abdominal vis- cera accompanying external trauma without production of positively in- dicative local or general symptoms. It is the imperative duty of the sur- geon to intervene provided there ex- ists even presumptive evidence of in- ternal damage. A properly executed celiotomy is practically devoid of clinical risk. Where visceral damage has occurred the mortality under ex- pectant treatment is nearly 100 per cent. F. T. Fort (Internal. Jour, of Surg., Sept., 1920). Report of a case of accidental shooting in which the bullet punc- tured the bowel 7 times and passed out of the abdomen at the side oppo- site of entrance. No attempt was made to evacuate the intestine. An incision was started at the point of entrance of the bullet and extended along its course for 7 inches. Each small hole in the intestine was re- paired by inverting the ragged edges into the wound and closing with a double row of Lembert sutures, pene- tration of the mucous coat being avoided. A small drain of iodoform gauze was left in the wound until the bowels had moved twice. Prompt recovery followed. Vertner Kener- son (N. Y. Med. Jour., S^pt. 7. 1921). Report of a case in which an opera- tion was performed 2 hours after a pistol wound of the right hypochon- drium. A tunnel wound of the liver was found, and was controlled by gauze packing. The gauze was re- moved on the fourth day and recovery followed. Another case, in a girl of 12 years, was operated upon 6 hours after the infliction of wounds. Five perforations were found in the small intestine. These were sutured. A cigarette drain was left in the cavity, and removed in 2 days. Recovery took place. Charles Farmer (Ky. Med. Jour., Sept 1921). Reaction. — As soon as reaction oc- curs in these cases another danger threatens the patient, that of hemor- rhage, which the state of collapse has so far prevented to a degree, unless an extensive injury has caused over- ABDOMINAL INJURIES (LAPLACE). 125 whelmingr exsanguination. In this event, however, the patient's recovery from the preliminary shock would hardly have taken place. Hence the necessity of closely watching the sufiferer. Cases of prolonged collapse some- times turn out to be trivial, while a short period of it may be the prelude to the most grave complications. The former cases are, unfortunately, rare, and profound shock of any dura- tion should be looked upon with sus- picion. This is especially the case when a second period of shock is passed through — the "relapsing col- lapse" of Bryant — indicative of a secondary hemorrhage or the giving way or separation of some damaged tissues. The condition after subcutaneous rupture of the abdominal wall may become very serious in a short time. Any surgical procedure instituted must be thorough, all intestinal le- sions being repaired, bleeding points checked, and blood-clots, when abundant, all removed. For the peri- tonitis arising from fecal material in the abdominal cavity good drainage with tubes must be established, with saline proctoclyEis and hypodermo- clysis, enterostomy and saline flush- ing of the bowel for intestinal pare- sis, and repeated stomach washing for vomiting and gastric distention. Dardanelli (Rif. med., June 8, 1912). That cases clearly showing by their history and the active symptoms a grave injury should be submitted to surgical measures as early as pos- sible will hardly be gainsaid in the light of our present knowledge. An equally positive conclusion, based on every means of diagnosis available, will alone warrant the assertion that no serious injury is present; but, if on the other hand, doubt exists, abdominal section will alone insure the patient adequate protection. If nothing be found, no harm will have been done if precepts governing asep- tic surgery have been closely fol- lowed ; if a rent in the liver, an intestinal tear or rupture, a serious hemorrhage be discovered and ade- quateh' dealt with, the patient will have received the benefit of all our art's resources. The seat of rupture being located, the nature of the injury will deter- mine the procedure to follow, linear enterorrhaphy being indicated in longitudinal ruptures, and circular enterorrhaphy in complete ruptures. These procedures are now generally preferred to an artificial anus. It is sometimes impossible to adjust ade- quately the edges of the wound, owing to the condition of the margin, and an omental graft must be used to cover the contused area so as to avoid a secondary perforation. Considerable extravasation of feces, blood, and other liquid or semiliquid material may have occurred into the peritoneal cavity. All chances for further contamination of the intes- tinal tract having thus been removed by closure of the rupture, the peri- toneal cavity should be carefully cleansed by flushing with warm, steri- lized water, a soft aseptic sponge being employed to mop gently all the surfaces that may, in any way, have come in contact with the infectious fluids. The cavity is then closed and free drainage insured. Satisfactory results are obtained even in cases in which very great in- jury and ample opportunity for infec- tion of all wounds have markedly compromised the issue. The after-treatment should be 126 ABDOMINAL INJURIES (LAPLACE). based upon the necessity of insuring rest for the intestinal tract for a few days. This may be carried out by administering- opiates. The patient's strength should be sustained by means of nutrient, but small and fre- quently administered, enemata. Under all circumstances, an abdom- inal injury should cause the patient to be watched several days. After an uncomplicated injury he should re- main in bed and be placed on a milk diet for a few days. Anodyne appli- cations over the abdomen and a little morphine, internally, if there is pain, is all that is usually required in these cases. In the less fortunate the pro- cedure to be adapted varies according to the organ involved. Intestines. — The probability of a rupture having been recognized, the abdomen should be opened by an in- cision through the linea alba, and any hemorrhage quickly arrested. The next step is to locate the visceral injury. Of importance in this connection is the fact that in the majority of cases the rupture is due to compression against the spinal column. The spot over the abdo- men upon which the blow carried being considered as the one end of an imaginary line and the center of the vertebral column as the otlier end, the probabilities are that the rupture will be found near the linear axis. Again, if the rupture cannot be readily found, hydrogen may be gently insufflated into the rectum, as advised by Senn, and the spot from which the gas escapes will indicate the location of the rupture, — approxi- mately, in the case of the small intes- tine, and accurately l)elow the ileo- cecal valve. Disorders, or lesions other than those sought after, are misleading conditions that should be borne in mind. Lesions of the jejunum are some- times difficult to locate. Stomach. — When the symptoms of complete tear are recognized, the presence of the organ's contents in the abdominal cavity render an imme- diate laparotomy imperative. The incision should include the tissues between the xiphoid cartilage and the um])ilicus. If the tear cannot be quickly found, repetition of the infla- tion with hydrogen-gas will help to locate it. As soon as located any bleeding vessel should be ligated, and the stomach evacuated and cleansed through the adventitious opening of any substance that may have re- mained in it. If the wound be a lacerated one, it may be necessary to pare its edges. This being done, the tear is closed, the mucous membrane being united with a continuous or interrupted suture, cut short, and the muscular and serous coats by the continuous Lembert suture. Closure of the laceration having removed all danger of further extravasation into the peritoneal cavity, the latter must be flushed with warm, sterilized water and mopped out with a soft sponge. The cavity is then closed and a drain left if the peritoneal sur- faces have been exposed to contami- nation for some time. Liver. — Especially when the history of the case seems to indicate the pos- sibilitv of a lesion of this organ is careful watching imperatively de- manded, owing to the violent hemor- rhages which they involve. Either this complication or peritonitis having been recognized, the abdomen should Lines of Incision for Abdominal Exploration and Operation (Laplace). 1, median line; 2, for liver and gall-bladder; 3, for pyloric end of stomach and duodenum; -1, 4', for upper abdomen, including stomach and pancreas; 5, for spleen; C, for tail of pancreas or greater curvature of the stomach; 7, umbilicus, median line; 8, 8', 9, 9', 10, 10', for intestines according to location of injury, 8 being the best for appendix as it severs no muscular fibers; 11, vermiform appendix; 12, McBurney's line; 13, cecum and ileum; 14, anterior superior spinous process of the ileum; 15, 16, 17, IS, defective incisions for appendicitis: they cut across deep muscular fibers: 19, 19', for inguinal hernia; 20, 20', 21, 21', for bladder according to location of injury. ABDOMINAL INJURIES (LAPLACE). 127 be opened at once in the middle line. The abdominal wound should be large enough, if possible, for the surgeon to see the liver, but in every case he ought to make a careful ex- ploration with his finger, especially directing his attention to the convex and posterior surfaces of the organ. When a rupture is found, the wound may either be cauterized, plugged, or sutured. Plugging with antiseptic or aseptic gauze seems to give the best results, one end of the gauze being left out at the angle of the abdominal wound. The plug should be removed not earlier than the forty-eighth hour, lest there should be a recurrence of the hemorrhage, and not later than the fourth day, lest a biliary fistula should be formed. When the bleed- ing is very severe, sponges mounted on holders appear to produce more- satisfactory pressure than simple plugging, which is, perhaps, better reserved for slighter injuries. Hot- water irrigation may be of advantage in these cases. A ligature should be applied to any large vessel which is seen to have been torn. Sutures are particularly useful when the lacera- tion extends deeply into the substance of the liver, since by their means the edges of the wound may be brought lightly together and the bleeding can be controlled. Drainage of the pelvic pouch, by an opening just above the pubis, serves best to give free pas- sage to subsequent discharges. The capsule should be included in the stitches. The prognosis is very un- favorable when peritonitis has oc- curred, but something may still be done to prevent the fatal issue by opening and afterward draining the abdominal cavity. In suturing the liver, the writer passes the needle, threaded with cat- gut, through a small wheel made ot fine silver wire. Each wheel, the diameter of which varies from 6 to 15 mm., has 8 spokes. A. L. Soresi (Riforma Medica, Mar. 2, 1917). In a case of traumatic rupture of the liver in a boy, aged 8 years, due to being run over by an automobile, the outstanding signs were the thor- acic type of breathing, the anxious expression, and the history of severe trauma. Normal urine was voided. When there is a possibility of a solid abdominal viscus being damaged, it is generally safer to explore at once rather than await the symptoms of hemorrhage. Doyle (Med. Jour, ot Australia, Jan. 10, 1920). Spleen. — After a simple contusion the spleen soon returns to its normal condition without further trouble, and a few days in bed, coupled with strapping of the side to limit motion, usually suffice. When, however, there is laceration of the parenchyma the convalescence is slow, abscesses following in quick succession. After a time these cease and recovery is im- interrupted. Symptomatic treatment, revulsion over the organ, and tonics may shorten the duration of such cases. When the symptoms do indicate that exsanguination of the patient is taking place, death will most prob- ably follow, although the hemorrhage is not as copious as it can be in tears of the liver, the splenic capsule being more elastic than that of the latter organ. Removal of the organ should be resorted to. The abdominal wall is opened by means of an incision through the left semilunar line and the peritoneum is freely opened. The hand being introduced into the cavity, all adhesions are torn up and the organ is brought to view. The 128 ABDOMINAL INJURIES (LAPLACE). vessels entering the hilum are then clamped and the organ is removed. The stump is ligated and, after spong- ing out the abdominal cavity, the wound is closed. Summary of cases of rupture of the spleen reported in literature: Unop- erated: Of 220 cases, 17 patients re- covered— mortality, 92.3 per cent. Operative results: Splenectomy, 67 cases, 38 patients recovered, 29 died — mortality, 56.7 per cent.; splenor- raphy, 2 cases, 1 patient recovered, 1 died — mortality, 50 per cent.; tam- ponade, 6 cases, 5 patients recovered, 1 died — mortality, 83.3 per cent. In the splenectomies, 13 patients had complicating injuries, of which 9 died. In 2 which recovered, the complications were unimportant. Ross (Annals of Surg., July, 1908). Kidney. — The majority of mild cases of perirenal extravasations of blood and urine recover as the result of rest and expectant treatment. The patient should be kept in bed and his diet limited to liquids, the best of which is milk; this beverage requires, besides, the least physiological labor from the injured organ. The nourish- ment of the patient may further be sustained by rectal injections of beef- tea, and these should entirely be resorted to if there is vomiting, the latter tending greatly to encourage hemorrhage. Details of 5 cases. The patients were men between 25 and 42, a woman of 30, and a boy of 12. Un- less there are signs of internal hemor- rhage, absolute repose and ice to the kidney region are indicated. The pa- tients were all dismissed in good con- dition after operative intervention. Yoshikawa (Beitrage z. klin, Chir., Jan., 1909). When hemorrhage occurs in the direction of the bladder, there is likely to be accumulation of blood- clots, which, if small, will readily pass out with the urine. Frequently, however, the clots are large and cause retention of urine and marked tenes- mus. A large catheter should there- fore be introduced and kept in situ when the hematuria is marked, and the bladder occasionally washed out with a weak boric acid solution. Median urethrotomy to remove clots and relieve retention sometimes be- comes necessary in these cases. When the symptoms do not improve under these measures, an incision should be made, exposing the seat of injury, the extravasation removed, and the parts restored to their normal conformation. According to Keen, hematuria is valuable only as showing the fact of rui)ture of the kidney, but not as a symptom by which to decide on operating. It is not the visible loss of blood by the bladder, but the easily overlooked, but far from dangerous, bleeding into the peri- nephric tissues, or into the peritoneal cavity, that should receive the chief attention. The dangers of rupture of the kidney are mainly hemorrhage and sepsis. When, therefore, the symp- toms are such as to indicate marked hemorrhage or sepsis, and especially if a tumor form quickly in the lum- bar region, an exploratory operation should at once be done. If severe laceration be present, or the kidney's functions be practically compromised, or the hemorrhage be such as to require ligation of the renal vessels, lumbar nephrectomy should immedi- ately be performed, primary nephrec- tomy being safer than secondary re- moval of the organ. When hematuria continues and a hematoma forms in the region of the ABDOMINAL INJURIES (LAPLACE). 129 kidney which seems to be increasing in size, and when there are symptoms of concealed hemorrhage, it is far better to operate then under good conditions than to wait until the risk is greatly increased. Even if the hematoma does not appear a hemor- rhage may be dissecting up tissues for a considerable distance, and then the evidence of concealed hemorrhage must take the place of evidence of a hematoma. The danger of an ex- ploratory operation is not great if it is undertaken before too extensive hemorrhage or septic infection has taken place. Frank Walker (Boston Med. Surg. Jour., May 24, 1917). Bladder. — WHien a patient presents the history of a severe abdominal contusion or crushing, followed by inability to micturate, the catheter should at once be used. The presence of hematuria will indicate a lesion in the urinary tract, kidney, or bladder. If the urine with- drawn is observed to be well mixed with blood and, instead of red, it ap- pear brown and smoky, the lesion is probably one of the kidney. If, on tile contrary, the urine be brig^ht red, the probability is that the bladder has been torn. In the latter condition the diagnosis may also be assisted by the quantity of fluid passed at a given time. If, when the catheter is intro- duced and after a history marked with shock, no urine is obtained, the chances are that not only the bladder has been ruptured, but that the laceration is extensive, the opening having allowed the vesical fluids to escape into the abdominal cavity. A free flow, on the contrary, would tend to show that the tear, if any exist, is small. Of course, the invagination of the intestines into the vesical open- ing, or a valve-shaped laceration, may cause the same favorable signs to exist, thus misleading the diagnosti- cian. Very small lesions may be present, sufiicient to allow the urine to escape, drop by drop, into the sur- rounding parts. Detection of them is very difficult, the subsequent com- plications alone showing the presence of extravasated fluids. The presence of any tear, except very small ones, may also be ascer- tained by injecting a weak boric acid solution into the organ, through the catheter. If a rupture be present, the bladder will not fill and rise above the pubis. Filtered air may be used for the same purpose, but it is less satisfactory, owing to the danger of secondary collapse. The urine may have passed into the prevesical connective tissue out- side the peritoneum, or the vesico- rectal or vesicouterine space, owing to a rupture in these locations. This constitutes the extraperitoneal lesion. Cellulitis and sloughing rapidly ensue without subsequent involvement of any organ in the neighborhood of the lesion, the vagina, the rectum, etc., the patient dying from septicemia. Death in intraperitoneal rupture of the bladder is due in a majority of cases to uremia and not to peritonitis. In most instances death occurs before the latter can develop. One should operate whenever there is suspicion of intraperitoneal rupture and not wait for evidences of a peritoneal re- action. Rost (Miinch. Med. Woch., Jan. 2, 1917). To ascertain whether a tear be extraperitoneal or not, a measured quantity of a weak boric acid solution is injected through the catheter. If the full amount is not recovered, the chances are that the rupture is extra- peritoneal. Report of a case of traumatic rup- ture of the bladder in which an un- i— S 130 ABDOMINAL IN7URIES (LAPLACE). usual feature was the obtaining of urine in considerable quantities after catheterizing the patient. The patient had been kicked on the lower abdo- men. The house surgeon passed a catheter and obtained about 10 ounces of blood-stained urine. Eight hours later 16 ounces of urine were drawn off. The bladder was washed out with boric solution, the solution re- turned being apparently the same in quantity as was injected. L. Gordon (So. Africa Med. Rcc, Feb. 28, 1920). Rupture into the peritoneal cavity, the intraperitoneal form of lesion, is less urgent as far as symptoms go. One, and even two, days inay elapse before active symptoms appear; but, when they do, rapid progress toward a fatal issue from general peritonitis is the rule. Uncomplicated contusion of the bladder readily yields to a few days' rest, the application of ice, and general symptomatic treatment. When, however, there is cause for suspecting a rupture from the nature of the accident or the violence of the blow, the catheter should at once be introduced. The presence of blood renders operative interference im- perative. After the rectum has been distended with a rectal bag an inci- sion three inches long is made in the middle line of the hypogastrium, beginning half an inch below the upper edge of the pubes, as in supra- pubic lithotomy. The peritoneum is then carefully rolled up, along with the prevesical fat. The bladder being thus exposed, search for the rupture is the next step. The rent is usually found along the posterior surface vertically down from the urachus ; frequently^ an extravasation of blood and urine indicates the spot. Occasionally, however, considerable difficulty is experienced, and opening of the organ is necessary so as to permit the in- troduction of the fmger, and thus allow of exploration of its inner surface. The rupture may be extraperi- toneal or intraperitoneal. If an intra- peritoneal laceration is found, the incision should be extended upward, the peritoneal cavity opened, and the cystic wound closed with fine silk by means of Lembert sutures, one-eighth of an inch apart, including only the peritoneal and muscular coats. The mucous membrane of the bladder should be respected. Important, in this connection, is the necessity of ascertaining that the sutures will hold; this may be done by distending the bladder with a lukewarm milk or an alkaline solution. The abdominal cavity is then care- fully irrigated and closed, leaving a drain if there is any possibility that fluids will accumulate in any of the surrounding tissues. Henry Morris holds that there is great danger in delaying operation in these cases ; the decomposition of the clots and the cystitis which is excited by their presence, as well as the fre- quent catheterization needed, exposes the patient to all the dangers of sup- puration of the wounded kidney, and also to the risk of infection. Patients who recover from extra- peritoneal rupture are more apt to suffer permanent disability than those who recover from intraperitoneal rup- ture, chiefly because of the urinary extravasation about the base of the bladder, inducing infection, necrosis, and loss of function. The treatment consists in drainage of the bladder either infra- or supra- pubicalh". Suture of the bladder tear is of less importance in extraperito- neal cases. For an associated pelvic ABDOMINAL IX7URIES (L.\PLACE). 131 fracture open operation wiring, etc., are unsatisfactory because of urinary infiltration. Indirect fixation by ex- ternal screws and clamps was found useful in a boy of 16, injured in a run- away. A Freeman's screw placed on either side of the symphysis pubis held the pubes in apposition until fibrous union was well established. The total mortality in all varieties of ruptured bladder treated surgically since 1900 has been less than 25 per cent. E. P. Quain (Surg. Gynec. and Obstet, xxiii, 55, 1916). Case of a man who had been kicked in the abdomen and jumped upon while intoxicated. The abdomen was rigid as in perforated duodenal ulcer; temperature. 102.5° F. (39.1° C); pulse, 1(X) to 110. Three ounces of clear urine had been passed. Upon incising the peritoneum there was a gush of blood-stained fluid, possibly 2 quarts. A tear in the bladder from the space of Retzius down to the tri- gone was found. The balance of the fluid was aspirated from the abdomen and the operation concluded by sutu- ring the rent in 3 layers, No. 1 chromic catgut being used first in the mucosa, the second layer including the muscular and serous coats and last the serous. A drain was placed in the pelvis and a catheter intro- duced through the urethra and fixed with a suture through the corpus spongiosum. The patient was placed in bed in the Fowler position with a Murphy drip. He was out of bed and voiding 16 ounces at a time on the tenth day. Erdman (N. Y. Med. Jour., Oct. 13, 1917). Case of a man struck in the lower part of the abdomen by the pole of a wagon. The symptoms continued for nearly five days before he came to the hospital. Temperature, 100° F. (37.8° C); pulse, 132; respiration, 12; white blood cells, 15,000; polynu- clears, IZ per cent. The abdomen was opened and 130 ounces of fluid ob- tained. A small transverse tear found in the upper portion of the bladder was sutured and the bladder drained below the paritoneum through a stab wound; the abdominal wound was also sutured and drained. Recovery was uneventful. E. F. Kilbane (N. Y. Med. Jour., Oct. 20, 1917). In retroperitoneal intestinal rupture from contusion operative treatment is especially difficult. In Zl cases of retroperitoneal rupture in the litera- ture, 29 cases were treated surgically, but in only 15 was the rupture dis- covered at operation. The surgeon may consider the condition due to retroperitoneal hemorrhage and close the abdomen with fatal results. Su- ture, though diflicult, can be done with hope of success in selected cases. G. Soedcrlund (Nordiskt med. Arkiv, li. No, 5, 1919). WOUNDS OF THE ABDOMEN. — Wounds of the abdomen may be non-penetrating, when the abdominal walls alone are injured, and penetrat- ing, when the peritoneum is included in the lesion, irrespective .of the in- strument (pistol, knife, etc.) with which the lesion is produced. Non-penetrating Wounds. — Non- penetrating- wounds are usually due to pointed cutting or blunt instru- ments. The lesions caused by a pointed in- strument, involving- the skin and muscles only, are usually very slight. With due aseptic precautions careful exploration of the wound with the finger may be resorted to if the visual examination does not suffice. Probes had better not be used, lest the wound be transformed into a penetrating one. Lesions caused by cutting instru- ments (knives, swords, etc.) vary in importance according to their depth and length. When the muscles are cut, the support for the abdominal organs is compromised, and ventral hernia may follow, unless great care be taken when the wound is closed. Lesions caused by blunt bodies 132 ABDOMINAL INJURIES (LAPLACE). (such as shot, glancing bullets, and fragments of shells, etc.) are usually attended by symptoms of contusions corresponding in intensity with the force of the blow. Severe laceration of the abdominal tissues may thus be caused and death occur from intes- tinal lesions. The hemorrhage attending these various kinds of wounds is usually slight. There is considerable ecchy- mosis, but this soon disappears. Oc- casionally shots or bullets become im1)edded in the abdominal tissues. The best sign of coexisting injury to one or more abdominal organs is rigidity, coupled, if there is abundant hemorrhage, with a small pulse, pallor, a pinched facies, and vomiting. Even slight abdominal trauma may entail severe symptoms, which, how- ever, gradually decrease in intensity, whereas if actual organic injury has been occasioned, their intensity con- tinues to increase. II. Riedel (Deut. med. Woch., Jan. 11, 1912). The writer lays stress on transmis- sion of the cardiac and respiratory sounds, so that they are audible over the whole abdomen almost as well as over the chest, as a sign of internal injury and positive indication for im- mediate laparotomy. This sign may already be present one-halt hour after the injury, never exists in extraperi- toneal injuries, has no relation to rigidity, and is ascribed to irritation of the parietal peritoneum through the outpouring of foreign material into the abdominal cavit3\ Claybrook (Surg., Gynec, and Obstet., Jan., 1914). Visceral extraperitoneal wounds showed symptoms more marked, lasting, and alarming than parietal injuries. The symptoms giving the impression of peritoneal penetration are: dullness over the liver, muscular rigidity of all or part of the anterior wall, vomiting, small pulse, facies ab- dominalis. stoppage of flatus and feces which persists more than twenty- four hours, retention of urine, and traumatic shock. Any one or more of these signs may show in an abdom- inal wall injury, but the occurrence of all together is rare. Before the war any of these symptoms would usually have been considered indicative of in- traperitoneal penetration. Tympa- nites was observed in 56 per cent, of the writers' series of extraperito- neal wounds. Stassen and Voncken ("Le peritoine en chir. de guerre," Paris, 1917). It is sometimes impossible without a lajiarotomy to tell whether a gun- shot wound of the abdomen involves the peritoneal cavity or not, for the signs and symptoms are not constant. It is first necessary to determine if possible the direction of the track. The absence of an exit wound does not necessarily mean that the foreign body is lodged in the abdomen. The facial expression is usually one of anxiety. Pain is not of great value, and may or may not be present. Tenderness is a very constant and reliable sign. Rigidity, or the ab- sence of it, is often most misleading. The pulse increases directly with the gravity of the intraperitoneal lesion, and gives an important basis for prognosis. Vomiting is usually pres- ent, but not necessarily. Thirst is a most distressing symptom. Roentgen- ray localization affords the most use- ful guide in the diagnosis of penetrat- ing wounds. Operation should not be undertaken before the patient has recovered from shock. In patients with shock and hemorrhage the au- thor has often waited six hours or more, taking the risk of further hem- orrhage, with results that justified the delay. Provided the patient is warm, operation is done at once, saline being given while he is on the table. Charles (Brit. Med. Jour., Mar. 23, 1918). Treatment. — After carefully arrest- ing bleeding, cleansing, and disin- fecting the wound, the tissues are united. Tn deep incised wounds the prevention of ventral hernia should ABDOMINAL L\7URIES (LAPLACE). 133 be borne in mind, and the cut mus- cular tissues broug"ht accurately to- gether by means of catgut sutures. This being done, silk sutures are also introduced and brought out to the surface, thus including the muscles and skin. Capillary^ drains are alone to be used, if drainage is at all neces- sary, larger drains affording oppor- tunity for the formation of a ventral hernia. The abdomen should be sup- ported by means of a bandage applied over the dressing and the patient kept in bed until complete repair of the wound has taken place ; from two to five weeks, as a rule. The bandage should be carried long after recovery, and the patient be warned of the danger he might incur by violent movement or strain. Penetrating Wounds, — The soft- ness of the tissues of the abdominal parietes causes them to be easily penetrated, and the organs within the cavity are all vulnerable for the same reason. The interstices between them occasionally allow the harmless passage of a weapon or bullet, but such cases are extremely rare. The missile may graze the perito- neum and barely miss it along with the deeper organs. Unfortunately wounds causing laceration of one or more of the abdominal viscera are the most frequent, and their fatalitj^ is proverbial unless a timely diagnosis allow of prompt protective measures. As is the case in contusions, the direction from which the missile or stab comes is of great importance. A bullet arriving from the side and striking near the linea alba would probably create a buttonhole wound or bury itself in the abdominal walls. A bullet coming from the front, on the contrary, would most probably perforate the organs in its axial line of flight. If the bullet has passed through the body an imaginary line between the entrance and exit will probably indicate the organs injured, including, of course, the peritoneum. Here again, however, the spinal column may cause deviation when the initial velocity of the bullet is small, and a deceptive line of injury furnished. To positively determine the course of a bullet is difficult in many cases. In stab wounds the opening is fre- quently of a sufficient size to permit prolapse of the omentum : an evident proof that the abdominal cavity has been penetrated. This rarely occurs in bullet wounds unless a large pro- jectile, or a bullet coming from either side of victim, has caused com- paratively large solution of continuity of the tissues. Prolapse of the omen- tum is most frequently observed in lesions of the left side. Coils of the small intestines are also frequently prolapsed and. in rare cases, the stomach, the liver, or the spleen has appeared between the lips of the wound. Symptoms. — As is the case after contusion, penetrating wounds of the abdomen may give rise to no symp- toms capable of affording any reliable clue to the extent of the internal in- juries. Profound shock may be pres- ent and no serious lesion exist. Severely injured individuals may, on the contrar}', present no acute symptoms and. perhaps, walk or ride a considerable distance before show- ing noticeable evidence of their condi- tion. Profuse hemorrhage alone gives rise to symptoms denoting a grave lesion : rapidly progressive exsangui- 134 ABDOMINAL IN7URIES (LAPLACE). nation or acute anemia; nausea or vomiting'; weak, rapid, and some- times irregnlar pulse; dilated pupils; cold sweats; yawning, ending- in con- vulsions and coma. Shocl< is likely to be progressive in these cases. The only symptoms that are present in practically all cases are pallor and vomiting: the accompani- ments of any severe blow on the abdomen, and therefore of no value whatever as differential signs. The temperature is of no assistance in these cases. The amount of "knock-out" after injuries sucli as will cause prolapse of the intestines is often surprisinglj' slight, subjects sometimes walking a considerable distance with such in- juries, with their intestines supported by a bandage. A man hit in the ab- domen may be quite unconscious that his intestine is prolapsed. Small mis- siles penetrating the bowel may cause very little immediate pain or disturb- ance; on the other hand, some men shot in the abdomen, or even the limbs, with a bullet or other small projectile, experience a tremendous blow' or kick which may induce un- consciousness. Intense pain occur- ring promptly in wounds of the lower abdomen is especiall}^ connected with penetrating buttock wounds, and is valuable in calling attention to their dangerous nature. Apart from very extensive injury, the shock in abdom- inal wounds seems due, in great part, to loss of blood and, later, peritonitis. Some superficial lesions on the outer surface of the liver seem, however, to cause extreme shock, sufficient to cause death without marked blood loss. Stripping up of tlie retroperi- toneal tissue by blood causes dispro- portionate collapse, possibly on ac- count of sympathetic injur}'. A small injury causing great pain will produce pallor and collapse with cold extremi- ties, though the pulse be quiet and good. Cuthbert Wallace (Pract., Sept., 1916). DIAGNOSIS.— On general prin- ciples dangerous complications are to be expected when marked shock, nausea, vomiting, hiccough, anxiety, intense thirst (indicating a probable involvement of the peritoneum), and insomnia are present. Besides these indications there are others peculiar to each organ which greatly assist in establisliing at least an approximately certain diagnosis. Intestines. — Bullets striking antero- posteriorly rarely cause more than four perforations, while oblique or transverse shots are likely to produce a much larger number of lesions: from fourteen to sixteen. On general principles, however, a jienetrating wound may always be considered as having caused a lesion of the intes- tines. The most important symptom is the escape of intestinal gases and more or less fluid substances through the wound. The mere presence of emphysema around the wound is of no value, however, since air is gener- ally forced into the wound by the bullet. The most experienced surgeons oc- casionally tind more or less difficulty in diagnosing penetration and perfor- ation before operation, and all are, of course, opposed to precocious operating in non-penetrating wounds. An aperture of exit is not always present. Any missile may ricochet, and the writer has seen wounds in which, if the missile had traversed by the shortest route between the two openings, there would have been per- foration of many vital organs and structures; yet there was no serious injury. There are a few^ recognized rules to follow: The closer together the wounds of entrance and exit, the less the chance of penetration. According to Rochard, if there is persistent com- ABDOMINAL INJURIES (LAPLACE). 135 plaint of abdominal pain, perforation is almost certain; if a patient passes gas at the anus, there is no perfora- tion. Eastman (Amer. Med. Assoc; N. Y. Med. Jour., Jan. 15, 1918). Pain is usually one of the first and most constant signs of injury to the abdominal contents, its character de- pending upon the amount of fluid escaping into the peritoneal cavity. Associated with pain is spasm of the abdominal muscles, especially the recti, which, even though slight, can usually be detected. Patients operated upon while in shock nearly always die, while in cases of active hemor- rhage they will die if not operated. The history and examination of the blood will help in the diagnosis, a leukocytosis being found in hemor- rhage but not in shock. McGuire (N. Y. Med. Jour., Sept. 21, 1921). Free hemorrhage from the wound tends to indicate an intestinal lesion ; if the stools also contain blood the diagnosis may be considered as certain. Probes have been discarded in penetrating wounds, owing to the irregular course followed by the bul- let in many cases and the danger of creating a false passage. Digital ex- ploration of small wotmds furnishes but little information, \vhile in bullet wounds there is danger of pushing into the peritoneal cavity what for- eign substances may happen to be present. The majority of surgeons now favor enlargement by an incision at least two inches in length, intersecting the bullet or incised wound. Layer after laver of tissue is carefullv dissected on each side of the track, the walls of which, in gunshot wounds, are usually darker than the normal tissues, owing to contact with the lead or powder- products of combustion. Using the grooved director to divide the tissues and the hemostatic forceps to grasp any bleeding vessel, the peritoneum is finally reached, when the certainty that a penetrating wound is present or not may be established. If prac- tised with strict aseptic precautions this procedure does not expose the patient. War injuries of the large intestine are serious from their infectivity rather than their multiplicity. They are often more difficult to find and repair than those of the small gut. In war, many extensive tears are caused by shell fragments, but a bullet may itself completely divide the intestine, as witnessed by Wallace in the case of the ascending, transverse, and de- scending colon, though not in the case of the pelvic colon. Many wounds are extraperitoneal or partly extra- and intra- peritoneal at the line of reflexion of the peritoneum of the colon. The latter variety of wound is often overlooked, in spite of care- ful search, and if found, is very hard to suture adequately. Stomach. — Hematemesis is a fre- quent symptom of penetrating wound of this organ and a much more A'aluable one than in contusion, since, in the latter, a slight laceration of the mucous membrane may produce it. The blood may be pure, but in the majority of instances it is mixed with partially digested alimentar}^ semi- liquid material. If the wound is suffi- ciently large to allow the contents to escape through it the nature of the injury is, of course, clear, but an important complication is to be ap- prehended : extravasation into the peritoneal cavit}- capable of causing peritonitis. If this is circumscribed, adhesions are formed and the patient recovers. Frequently, however, gen- 136 ABDOMINAL INJURIES (LAPLACE). eral peritonitis follows, ending in death. Hence the importance of an early recognition of extravasation. Besides hematemesis and the pres- ence of gastric fluids, there are usually present in such injuries the marked symptoms witnessed in cases of contusion : rapidly progressive anemia, pallor, fluttering pulse, etc. Gastric wound cases show pain, sick- ness, collapse, abdominal rigidity, and tenderness, vomiting being especiallj- pronounced, but the collapse less marked than usual. The respiration rate increases more rapidly in pro- portion than the pulse rate. Pain is worst when the pyloric or cardiac ends are involved, and collapse most marked in wounds of the curvatures. Eraser and Bates (Brit. Med. Jour., Apr. 8, 1916). The writer cites 2 instances in civil life where a single bullet made 3 per- forations in the stomach. This is due to the 3 contraction waves, each of which becomes quite deep as it passes toward the pylorus, thus mak- ing it possible for a bullet to graze or even perforate the tip of an in- verted crest as it passes through. N. Kerr (Ills. Med. Jour., xxxiii, 267, 1918). Liver. — A wound of the liver gives rise to all the symptoms observed when a contusion has caused lacera- tion of the organ : Intermittent pain, radiating in various directions, espe- cially toward the shoulder, if the convex portion of the organ is torn, and in the direction of the waist, if the concave or inferior portion of the organ is the seat of injury. There is marked pallor, superficial itching, and, later on, jaundice. The stools may be clay-colored, thus indicating the absence of bile. The hemorrhage varies in these cases according to the cause of the lesion ; one caused by a bullet is prone to be accompanied by consider- able and frequently fatal bleeding.' Stab wounds, when the weapon is not large, do not give rise to considerable hemorrhage. A copious flow of blood from a wound in the hepatic region indicates that the liver is involved. The flow of bile through the wound is a valuable sign, but it is seldom that this secretion can be obtained alone, blood being usually mixed with it. Of 2S cases of hepatic injury occur- ring in New York hospitals, uncom- plicated by serious lesions of other ab- dominal organs, 12 were ruptures, 9 gunshot wounds, 4 stab wounds. Eleven deaths resulted — a mortality of 44 per cent. (Tilton). Among 37 cases, the course of the missile was transverse in 21. Simple furrows often cause more trouble- some hemorrhage than perforating wounds. Shell wounds, usually ex- tensive, often cause secondary hem- orrhage, and are nearly always badly infected, necrosis and sloughing of a great part of the liver following, as a rule. With an open shell wound suppuration is the rule, but is of no great importance. Secondary ab- scesses, however, are a grave matter. Of the 37 cases, 25 showed compli- cating pleural injury; next came in- juries of the stomach. Seven cases showed no physical signs of liver in- jury. Secondary bleeding (4 cases) usually occurs about the tenth day and always means septic infection, which causes pain, distention, fever, and rapid, weak pulse. Twelve cases showed jaundice. Some form of bi- liary fistula — the most characteristic sign of liver injurj- — was present in 15 cases, opening through the pleura in 7, all of which recovered. Of 25 deaths from hepatic injury,. 60 per cent, were due to sepsis and 40 per cent, to secondary hemorrhage. The chief lethal complication was hemo- thorax; 7 cases died from infection ABDOMINAL INJURIES (LAPLACE). 137 from the effusion. G. H. Makins (Brit. Jour, of Surg., iii, 645, 1916). In some instances extensive lacera- tions of various organs may give rise to no preliminary morbid phenomena. Thus, W. L. Robinson reported fatal cases of marked laceration of liver and bowel in which there was neither shock, hemorrhage, nor high pulse. Spleen, — In cases in which the spleen is wounded the diagnosis can easily be established by the location of the external opening and the direc- tion of. the track. As is the case in contusion, there is marked local pain and profuse bleeding, which, if the organ is greatly lacerated, may soon prove fatal. This is apt to occur after gunshot wounds at close range, the organ under such circum- stances becoming pulpified. Punc- ture wounds are less likely to produce fatal hemorrhage. Pain in the left shoulder has been considered a diag- nostic sign of value. The diagnosis of splenic wounds is always difficult. Almost never, in the first few hours after the injury, is there the least sign of bleeding, un- less there is a crushing injury with tear of _ the pedicle, causing death within a short time. On the second to the sixth day, as a rule, the pulse suddenlj^ becomes frequent and weak, signs of anemia become marked, and the subject unexpectedly succumbs. Dullness in the splenic region or lower in the abdomen due to blood is inconstant and difficult to make out. Some splenic wounds exhibit symptoms of peritonitis. The diag- nosis is best based on the nature, site, and direction of the wound. Radio- scopy is significant if it reveals a foreign body that has penetrated to a depth of 7 to 12 centimeters from the posterior wall. Even in doubtful cases celiotomy is indicated, with splenectomy whenever practicable. J. FioUe (Paris med., Aug. 25, 1917). As a rule, injury of the spleen can be merely suspected, as tears of the liver, pancreas, and mesentery often present the same symptoms. The general signs of internal abdominal injury are not, as a rule, well marked at first. A slight hematuria, due to simultaneous slight injury of the left kidney, may help in the diagnosis. It is better to operate once too often than once too late. The best incision is the median, for in internal hemorrhage any organ may be in- volved. If necessary, a transverse incision may be added. If there are tears extending deep into the paren- chyma the spleen should be removed. In superficial tears of the capsule it should be tamponed, as suture is al- ways unceitain. In all of his cases the writer col- lected the blood from the abdominal cavity, mixed it with 0.5 per cent, sodium citrate solution, and reinjected it intravenously. He thinks he thereby saved many lives. H. Hauke (Beitr. z. klin. Chir., cxxii, 389, 1921). Kidneys. — Symptoms frequently accompanying wounds of the abdom- inal organs — extreme pallor, weak pulse, cold extremities, nausea, and vomiting — are apt to be- most marked Avhen, besides the organ itself, the peritoneum has been pierced. A wound of the kidney gives rise to severe pain in the majority of cases, but this symptom may be absent. As in cases of laceration, the pain radiates in various directions, especially in the direction of the ex- ternal genital organs. The testicle of the corresponding side, besides being the seat of considerable suffering, is frequently raised by spasmodic con- tractions of the scrotum. At first a small quantity of bloody urine may be passed, but this is often followed by vesical tenesmus and complete retention, due to the pres- ence of clots in the bladder. 138 ABDOMINAL IN7URIES (LAPLACE). Much information is sometimes ob- tained by a close examination of the wound of exit. If the track of the bullet be anteroposterior and the missile have entered from the front and penetrated the kidney, the exit wound will be found in the lumbar reg-ion. It is frequently found in this situation to contain urine, a positive indication that the organ or its annex, the ureter, has been wounded. In irjuries of the kidneys, simple perforations are often negligible. Hematuria, rarely severe or persist- ent, was observed in only 11 out of 21 cases. Its degree in no way ac- cords with the severity of renal dam- age. External escape of urine was noted in only 7 cases. In 17 fatal cases, 7 were due to secondary hem- orrhage, which occurred in 12 in- stances, usually about the fourteenth day. In every case of secondary hemorrhage the urine was infected. The hemorrhage occurred either as a persistent hematuria or a perirenal hematoma travelling into the iliac fossa and along Poupart's ligament, with skin ecchymoses and slight fever. Makins (Brit. Jour, Surg., iii, 645, 1916). Cystoscopy was employed in a number of cases to determine loss of renal function and in latent cases, the presence of bladder injury. The X- rays were used to advantage to de- termine the presence of and locate accurately missile fragments. The complications seen included sepsis, secondary hemorrhage, and urinary fistula. The last occurs when there is a wound of the pelvis, or the tear in the parenchyma extends into the pelvis, or when the ureter is torn. The chief causes of death were sepsis and secondary hemorrhage. Of 42 cases studied, 5 died. A. Fullerton (Brit. Jour, of Surg., Oct., 1917). The conditions which make an iso- lated kidney wound dangerous are hemorrhage and infection. In 46 fresh kidney wounds severe hemor- rhage was observed in 6. In 3 of these cases where there was a con- comitant liver wound, the patients died. In 3 of the cases the hemor- rhage was a hematuria; 2 died with- in a few hours. In 5 cases a peri- renal hematoma was produced. Of 35 remaining patients who showed no special symptoms necessitating immediate action, a primary opera- tion was done in 11 cases, a second- ary operation in 2, and abstention was observed in 22. The primary operation consisted either in a ne- phrectomy or in cleansing and drain- age of the trajectory. Of 3 nephrec- tomized cases, 2 died; of 4 tamponed patients, 3 died; 1 hematoma drained recovered; 5 clearance and drainage operations recovered; 22 abstentions from surgical intervention gave 3 deaths and 19 recoveries. M. Chev- assu (Bull, et mem. Soc. de chir. de Paris, xliv, 81, 1918). If the wound of entrance be in the back, its location over the site of the kidney may suggest a lesion of the latter; but the urine test will only be of value if the projectile only pene- trate the kidney without perforating it If it penetrate the organ, the ex- travasation will take place into the peritoneal cavity. The same will be the case if the missile enter from the front without going through the organ. Bullets buried in the renal parenchyma eitlier become encysted or cause abscesses, and pass out through the ureters or into the ad- joining parts. Bladder. — The symptoms van»^ ac- cording to the location of the wound. A perforation between the symphysis and the peritoneum above does not give rise to general symptoms ; whereas shock, pallor, weak pulse, vomiting, etc., may be much marked when the peritoneum is involved in the injur}'. In all cases, however, severe pain is experienced at the site ABDOMINAL INJURIES (LAPLACE). 139 of the lesion and radiating to the thighs and testicles. The passage of urine soon becomes very difficult and spasmodic. It may be voided, drop by drop, for a long while, notwithstanding the efforts of the patient, then suddenly gush out for a few moments and again flow slowly. This symptom may be due to accumulation of clots or to spasm of the urethra. If the catheter is passed, hematuria becomes evident when the bladder has been pene- trated : a characteristic sign. As in the case of rupture due to contusion, infiltration may take place through the wound into the neighbor- ing tissues ; any obstacle to the free passage of urine greatly encourages this. Hence the necessity, in all bladder lesions, of keeping the organ as free as possible by the frequent use of the catheter. The writer in a study of 53 cases calls attention to the comparative rarity of injuries of the bladder in warfare, the percentage of total wounds reaching the base being not more than 1 in 3000 or 4000. The bladder in a collapsed state occupies so little, space that it forms a very small target for the missiles of war. Just before an attack the nervous tension presupposes an evacuation of the bladder contents. If the patient is caught unawares at other times, the organ may be in a state of dis- tention. The prostate because of its proximity to the neck of the bladder is frequently injured with it. In the S3 cases reported, the in- jury to the bladder was caused by bayonet in 2 cases; by shell in 24 cases; by bullets (rifle or machine- gun) in 12; in 7 by shrapnel; in 1 case indirectly by a shell and directly by a fall of earth on the abdomen; in 7 cases the nature of the missile was unknown. In nearly 75 per cent., therefore, there was a wound in the buttock region reaching as far as, or actually penetrating, the bladder. The suprapubic route was compara- tively rare. The foreign body was retained in 33 cases. In 10 it came to rest in the bladder. In the remaining cases it lodged in the pelvis or its walls, oc- casionally between the bladder and rectum. The entrance wound is fre- quently of small size and compara- tively insignificant on superficial ex- amination. The wound in the blad- der itself was of the most varied nature, a perforation, tear or slif, and in 1 case a considerable portion of the bladder wall had been shot away. The gravity of bladder injuries is greatly enhanced by associated dam- age to adjacent structures such as intestine or bone. Shock is likely to be present when other severe injuries complicate the case. According to Wallace, it is one of the chief causes of death at the clearing stations. Hemorrhage also contributes largely to the high mortality of such wounds. Leakage of urine is one of the most important complications. This may appear at the wound in the parietes, or be more or less concealed in the form of extravasation into cellular tissue or leakage into the peritoneal cavity. In cases reaching the base, a urinary fistula was most frequent in the region of the buttock. A sudden, sharp pain may occur when the bladder is struck, but when the patient reaches the base, this pain is not a constant feature. There is some tenderness and rigidity in the hypogastrium in a fair proportion of the cases. Vomiting is occasionally seen in cases in which the peritoneal coat is intact. On the other hand, it may be entirely absent in the first hours of an intraperitoneal lesion. As in most war wounds, fever is com- monly present, and depends largely upon the amount of infection in the soft parts and bone. The mortality in bladder wounds is rather high. Wallace states that in uncomplicated cases it is 56 per cent.. 140 ABDOMINAL INJURIES (LAPLACE). and in complicated cases the picture complications which greatly reduce is dismal in the extreme. In the ^|-,g chances of recovery. writer's series of 53 cases, the nior- ^^ important factor is the time tality was over 24 per cent. A. Ful- i • i . -i -^4- : *v,« , . /T, -x AT 1 T ■ oA ioi8\ elapsmp- between the receipt of the lerton (Bnt. Med. Jour., vi, 24, iyi«). i fe f injury and that at which competent PROGNOSIS.— Gunshot wounds treatment is applied in mild cases, are more fatal than stab wounds, but ji-,5g jg especially true as regards the stab wounds, in which the peritoneum g^j.|y utilization of surgical measures is penetrated, are fully as fatal as gun- ^^.^^^ ^^^^^^ become necessar>'. The shot wounds. sooner these are instituted, the more The kind of weapon inflicting the favorable the prognosis, especially injury plays an important role in this ^i^ring the first ten hours, connection. A triple-edged bayonet jj^g relation between spontaneous is more likely to produce a serious cures and operative interference as laceration than a flat blade. Again, ^vorked out by Eisendrath is about as wounds caused by small weapons, fallows: — such as a Flobert rifle, for instance, spontaneous Recoveries. would hardly produce lesions to be p^.^ j-ej^t. compared to the old Enfield or Minie Spleen 15.8 rifles, which sometimes caused a large Liver 21.8 portion of an organ to protrude Intestines 7. ^, 1 If •. .1,^ e;^« /^f Kidney (extraperitoneal) 70. through a wound of exit the size ot ,• . ■, n n •^ Kidney (intraperitoneal) t>. an apple. Bladder (intraperitoneal) 2. Report of 44 cases of penetrating Bladder (extraperitoneal) IL abdominal wounds, all in civil prac- Operative Recoveries. tice. Of 6 cases without laparot- j.^.^ cent. omy 4 died. Among 38 penetrating 5^ ^jq cases). wounds the mortality was 45 per ^(^^ ^^7 cases). cent.; among 31 penetrating wounds 4^ ^43 cases prior to 1896). of hollow viscera, 5L5 per cent.; 50 (33 cases since 1896). among 25 gunshot wounds of hollow gQ viscera, 60 per cent., and among 6 ^qq ^ ^ cases). stab wounds perforating hollow vis- 52. (43 cases). cera, 16.3 per cent. Of 7 cases of 30 (i^gt 15 years).— Mitchell. injuries of the liver, spleen, and other - ,-. -n • j 1 • structures, with no involvement of In 1917, RoUVilloiS and his asso- hollow organs, 6 recovered. Stomach ciates presented the following figures perforation occurred in 11 cases, with concerning abdominal war wound 5 recoveries, and intestinal perfora- ^^^^^ treated in a I'Vench automobile tions in 29 cases, with 15 recoveries. . , T> J 1 1 -ix-- 1 ri A^,^,- surgical ambulance: — ^ Randolph Winslow (Jour. Amer. t. Recoveries. Med. Assoc, Oct. 3, 1914). per cent. Portions of the solid viscera are Small intestine (39 cases) 28.3 sometimes cut off or shot off, leaving Cecocolon (17 cases ) 41.2 ... , Liver (7 cases) -«o a gaping tear, which greatly com- stomach (6 cases) 66.7 promises the issue. Again, as is Spleen (2 cases) 50.0 often the case with the liver, the Hemorrhage is a great enemy of bullet, or any foreign material the wounded subject in abdominal dragged in by the latter, may lead to wounds, owing to the fact that there ABDOMINAL INJURIES (LAPLACE). 141 IS Tittle tendency toward spontaneous arrest. Three or four hours after an injury small arteries in wounded bowel are still spurtint? vigorously. Hence the necessity and value of rapid transportation of these sufferers to a suitaljly equipped operating room. H. H. Sampson (Brit. Med. Jour., Apr. 11, 1916). Much bleeding occurs from injured gastric vessels, omentum, mesentery, retroperitoneal tissue, abdominal wall (deep epigastric artery), pelvic veins, liver, kidney, and spleen. The intes- tinal walls, on the other hand, do not bleed to any appreciable amount. Pallor and pulse are the best criteria as to the blood lost. If near a wound in the bowel, bleeding may aggravate the situation by carrying infection to distant parts of the abdomen. Retro- peritoneal infection may occur with or without a wound of the bowel; where the bowel is injured, the colon is usually the part implicated, the en- trance wound being on the flank or loin. From retroperitoneal gas infec- tion the peritoneum may be pushed forward as in retroperitoneal hemor- rhage; such cases are nearly always fatal. The operation site, too, be- comes badly infected in many in- stances of penetrating abdominal wound, the origin of acute infection being in the peritoneal cavity. Vir- ulent wound sepsis may occur even after a lesion of the small bowel has been successfully dealt with by the surgeon. Death from peritonitis in abdominal wounds usually occurs on the third to fifth day, but may occur within 24 hours or in 10 days. The degree of bowel distention is a better prognostic guide than the amount of exudate present. Wallace (Pract., Sept., 1916). In abdominal wounds the mortal- ity, excluding moribund cases, was 50 per cent. The total operative mortality was 54 per cent. That of hollow viscera, 65 per cent.; of stom- ach, S3 per cent.; of small intestine, 66 per cent.; and of great intestine, 59 per cent. Among 263 abdominal wounds at an advance station, the patients oper- ated on between 1 to 6 hours after wounding were 43; recovered, 27, or 62.8 per cent.; died, 16, or 37.2 per cent. Cases operated 6 to 12 hours after wounding, 33; recovered, 12, or 36.3 per cent.; died, 21, or 63.7 per cent. Patients operated on between 12 to 16 hours after wounding, 18; recovered, 3, or 16.6 per cent.; died, 15, or 83.4 per cent. Patients oper- ated on over 24 hours after being wounded, 11; recovered, 5, or 45.4 per cent.; died, 6, or 54.6 per cent.; re- coveries at 48, 36, 33;/2, 32 and 30 hours, respectivel3\ Wallace (Lancet, Apr. 28, 1917). Report on 263 cases of abdominal wounds encountered at a hospital stationed close up to the fighting line and thoroughl}' equipped for dealing with urgent surgical work. Recov- ered, 136, 51 per cent. Died, 127, 49 per cent. Number admitted ''with penetration," 180. Number on whom a laparotomy was performed, 110. ■Recovered, 46, 41.5 per cent. Died, 64, 58.5 per cent. Hughes and Rees (Lancet, Apr. 28, 1917). Of the patients who survive opera- tion performed in the first twelve hours a high proportion will have had their lives saved by it, and this is true in a lesser degree of those oper- ated on in the second twelve hours. After this time most of those who survive operation are those whose injuries were not originally fatal. Owen Richards (Brit. Med. Jour., Apr. 27, 1918). Report of the case of a man in whom a steel rod one-half inch in di- ameter and 54 feet long, in falling, entered the body just behind the left shoulder and emerged at the inner aspect of the right knee. After pass- ing through the posterior aspect of the left lung, the rod penetrated obliquely through the bodies of 3 or 4 vertebrje in the lower dorsal and upper lumbar regions. Below this it could be felt below the pole of the right kidney and just behind the in- ferior vena cava. At this point it passed for about one-half inch into 142 ABDOMINAL INJURIES (LAPLACE). the peritoneal cavity without causing any damage, and again became extra- peritoneal by penetrating the psoas muscle. It appeared to leave the ab- dominal cavity by drilling a hole through the brim of the pelvis behind the acetabulum. Recovery from the shock was rapid. The upper end of the rod having been sterilized, trac- tion was applied in the direction of the curvature of the rod, which was thus slowly removed while a close watch was kept for internal hemor- rhage, etc. The resulting shock was great but yielded to treatment. Un- eventful recovery followed. Lake (Lancet, Apr. 23, 1921). Intestines. — The jirof^nosis depends greatly, upon the nature of the lesions. Stab wounds opening- the intestine lengthwise, if small, often heal of their own accord ; transverse wounds are more serious, while complete sec- tion of the bowel is a very dangerous complication. Gunshot wounds show a great fatality. Prior to the intro- duction of antiseptic surgery the mortality exceeded 90 per cent. ; since then, the mortality has been reduced to 40 per cent, or less in cases oper- ated during the first twelve hours. Perforated wounds of the descend- ing colon and sigmoid flexure are seldom fatal ; those of the transverse colon give a worse prognosis, by the formation of fistulae, adhesions, and abnormal communications. Again, diatheses may compromise recovery. The authors noticed that the less the damage to the gut — when the lumen had been entered — the greater the likelihood of extensive peritoneal soiling; this is ascribed to the inhibi- tion of peristalsis in massive injuries, which is incomplete or absent in the lesser ones. Fraser and Bates (Brit. Med. Jour., Apr. 8, 1916). Infection of the small and large bowel exhibit a radical difference in that, whereas the former tend to spread progressively, the latter if un- disturbed, tend to become localized. As regards the small intestine, there does not seem to be much danger of infection in the first few hours, but a critical period would appear to be at the eighth to the twelfth hour. The infection does not usually result from extrusion of the bowel contents, for the viscus is generally empty and paralyzed, but probably from the carrying out of infection by the pro- jectile and the everted mucous mem- brane. For some hours the coils stay in the position in which they were when wounded. At a later period they are found, on the contrary, thin and distended, due to beginning in- fection. Small gut injuries, as a whole, are serious from their multi- plicit}\ The lesions vary from a small perforation to complete divi- sion or destruction of a part of the bowel. Bomb wounds, small though often multiple, are favorable, usually lending themselves well to suture. Bullets cause all sorts of injuries, often as severe as those due to larger shell fragments. Wallace (Pract., Sept., 1916). Septic infiltration of retroperitoneal tissue seems a frequent lethal factor in large gut wounds. Wounds of the transverse colon are more apt to be multiple than those of the other divisions of this gut. Wounds of the rectum are divided into those compli- cating wounds of the buttocks, ischial fossae, or perineum, and those causcJ by missiles entering the lower ab- domen. With the former the great- est danger is septic absorption, but, on the whole, extensive buttock wounds do not do badly at the front, being widely open from the nature of the injury. With the abdominal type, severe multiple injury of the small bowel, and also injury of the bladder, are likely to accompany the rectal wound. Septic peritonitis is to be feared. Wallace (Lancet, Mar. 4, 1916). Stomach. — Uncomplicated wountis of this organ frequently yield without ABDOMINAL INJURIES (LAPLACE). 143 trouble when the bullet, blade, or other instrument causing the perfora- tion is small, especially if the stomach was empty at the time the injury was inflicted. The mucous membrane bulges out and forms a plug which obturates the hole until reparative processes have sealed the aperture on the peritoneal side. Complicated cases, in which the lesions are exten- sive, soon reach a fatal issue if de- prived of timely surgical intervention. Many cases of injury limited to the stomach have died, after successful suture, from the efifects of primary gastric hemorrhage. The escape of food from the wounded stomach de- pends not only on the time of the last meal, but also on the size and situa- tion of the wound. If the wound is small and near the lesser curvature or cardiac end, little food escapes, while if it is large and near the greater curvature, marked extravasation may occur. Liver. — The prognosis of wounds of the liver depends mainly upon the complications. If the patient does not die from heinorrhage soon after the receipt of the injury, he is still exposed to the results of extravasa- tion into the peritoneal cavity, the presence in the liver of a foreign body, — the bullet and what material it may have forced into the wounds, — etc. Peritonitis, hepatitis, and ab- scess are, therefore, dangers to be taken into consideration. Hepatitis and abscess are much less to be feared, however, from stab wounds, no foreign body being left behind, unless, as in dueling, the sword-point strike the spinal column, causing the blade to break. In such an event, however, the hemorrhage would probably prove mortal very rapidly. As to mortality, the statistics of Edler, Mayer, and others show it to average about 50 per cent., including the cases attended by complications. The most extensive injuries to the liver are frequently not incompatible with life. One patient who recov- ered lost a transverse section of the entire upper abdominal wall some 3 inches in width, with a groove in the liver substance which almost bi- sected it. The lower half of the liver was stitched into the defect in the abdominal wall. R. E. Skeel (N. Y. Med. Jour., Oct. 18, 1919). Spleen. — Slight punctured wounds of the spleen are not mortal unless complicated with laceration of a large artery. They are sometimes followed by abscesses which heal after a pro- longed period in the great majority of cases. Severe punctured wounds are dangerous in proportion, but, if the primary hemorrhage is not such as to cause an early fatal issue, the chances of recovery are about those of slight wounds. Gunshot wounds are much more serious as a result of rupture of the spleen taking place under the con- cussion. When the bullet is large and its velocity is great, fatal hemor- rhage quickly ensues. Rupture of the spleen may also occur during convalescence. During the War of the Rebellion the proportion of deaths was 93 per cent. In civil life, however, the weapons used are, as a rule, less powerful, and the mortality is much smaller. In the European war a mor- tality as low as 37.5 per cent, in 8 cases was reported by Duval. The predilection of this organ for abscess tends to compromise recovery. Kidneys. — Complications are also to be feared in lesions of this organ. 144 ABDOMINAL INJURIES (LAPLACE). namely : peritonitis, nephritis, and secondary hemorrhage. Again, the position of the kidney makes it prob- able that other organs are also injured in the majority of cases. The direc- tion from which the bullet or stab came, the length of the penetrating blade, etc., are important factors when the nature of the injury is to be determined. Bladder. — Gunshot wounds of the bladder are always serious as far as complications are concerned, rectal, vaginal, perineal, and scrotal tistuhx being very frequent. As to the mortality of penetrating wounds of the bladder, it is not so great as in lesions of any of the other abdominal organs. Stab wounds are more frequently mortal than uncom- plicated bullet wounds, the propor- tions being 29 per cent, in the former and 17 per cent, in the latter. When, however, osseous lesions are also present, penetration or fracture of the pelvis, etc., the mortality reaches 29 per cent. TREATMENT. — The preliminary measures indicated in the treatment of complicated contusions of the abdomen are also applicable in that of penetrating wounds of that cavity. Protrusion of portions of the intes- tines, the mesenterv'. and the omen- tum through the external wound is an early complication met with in many cases of penetrating wound. If the protruding mass be intestinal and in good condition it should at once be returned into the abdomen. An easy way of accomplishing this (recom- mended by Levis) is to raise the middle of the patient's body by means of a pillow, the hands, etc., while he is lying on his bock. The anterior portion of the pelvis is thus separated to an abnormal degree from the anterior portion of the thorax, and the increased room in the abdominal cavity thus obtained causes the intes- tines to .spread out, as it were, and, their weight causing traction upon the protruding loop, the latter quickly slips in. At times the accumulation of gas or fecal matter checks its inward progress ; the gas can easily be let out bv inserting a clean hypodermic needle into the projecting bowel; the fecal matter can also be reduced in quantitv bv drawing out an addi- tional portion of the gut — thus in- creasing the size of the loop — and gently pressing small portions of the contents into the unprolapsed bowel, thus diminishing the tension of the protruded mass. It is sometimes necessary to enlarge the abdominal wound. If the projecting mass be greatly inflamed the latter procedure is unavoidable. If it be gangrenous it had better be incised and the forma- tion of a fecal fistula permitted. An omental protrusion, if healthy, can be immediately returned, but if greatly inflamed or gangrenous it should be transfixed near the abdom- inal wall and tied with a double liga- ture; then excised. The stump is then secured in the deeper portion of the wound with ligatures and adhe- sive strips. Punctured wounds of the abdomen are frequently recovered from spon- taneously, owing to the absence of serious visceral lesions. The same statement may be made as re- gards bullet wounds, but with less emphasis. Of serious abdominal injuries 20 per cent, are hopeless, and of the re- maining 80 per cent., not less than ABDOMINAL LXJURIES (LAPLACE). 145 60 per cent, should recover after early operation under proper conditions. Rutherford Morison (Oxford War Primers, 1915). Surgeons are agreed that wounds of the small gut area should be ex- plored. There is still some doubt, however, about cases of suspected stomach injury and of wounds appar- ently involving the colon. Wounds limited to the liver furnish most of the cases of undoubted penetration which it is advisable to leave alone; the kidney and spleen furnish a few of these. While hemorrhage is itself a sufficient reason for operation, espe- cially if the case is seen early and the bleeding presumably continuing, the many cases presenting a single entry of a missile, particularly in the back, buttocks, thighs, and lower thorax, without signs of bleeding, are per- plexing to the surgeon. If the latter does not feel justified in operating on principle, he must watch the pulse and the abdominal rigiditj'. As a rule, within 4 or S hours the abdomen will harden or the pulse rise above 100. or both, if the intes- tine has been wounded, thus indicat- ing operation. In lower thoracic wounds the abdominal rigidity must be discounted, but in suspicious thigh and buttock wounds, rigidity and rapid rising purse are urgent signals for operation. Single wounds of the posterior aspect of the flanks present many difficulties. Since a median in- cision to explore the small bowel in such cases maj' lead to dissemination of a previously local infection about the colon, possibly the best course is a local exploration through a transverse loin incision, or a careful watch for abdominal involvement. With regard to stomach wounds, Wallace favors routine operation on account of the danger attending hem- orrhage from vessels supplying this organ. Withholding operation, the favorable moment for dealing with this hemorrhage may be passed be- fore the signs of anemia appear; or, there may be associated lesions of other organs that will prove fatal. Cuthbert Wallace (Pract., Sept., 1916). Report on 56 non-military cases of stab and gunshot wounds of the ab- domen, mostly revolver wounds. Severe lacerations of internal organs, such as are observed in war wounds, were not found. There were 35 per- forating wounds with injuries to in- ternal organs, with 8 deaths, and 10 perforating wounds without injury to internal organs and 11 non-per- forating wounds without any deaths. Immediate, careful transport of the patient should follow the application of a compression bandage. Every wound of the abdominal wall should be widened as early as possible in order that it may be determined whether the peritoneum is involved. If so, laparotomy is indicated. The positive indications for opera- tive treatment are: (1) Extrusion of abdominal organs; (2) escape of gastro-intestinal contents or urine from the external wounds; (3) severe anemia, with an increasing zone of dullness indicating severe hemor- rhage; (4) X-ray demonstrations of the escape of gas into the peritoneal cavity. W. Smital (Wien. med. Woch., Ixx, 653, 1257, 1305, 1442, 1501, 1547, 1601, 1920). When surgical measures become necessary, including- enlargement of the wound, the patient should be placed under an anesthetic. The rectum should be emptied by copious injections containing a tablespoonful of glycerin to the pint. A subcu- taneous injection of morphine (^ grain) is generally recommended. Rectal injection of whisky and warm water, 2 ounces of the former and 4 of the latter, is useful to sustain cardiac action. It may be repeated in an hour if evidences of impending shock are still present. In patients with nervous shock or severe hemor- rhage, camphorated oil, ether, and saline injections with %o grain (0.001 1—10 146 ABDOMINAL INJURIES (LAPLACE). Gm.) of adrenalin have proven useful. Intravenous saline infusion may be continued during the operation. It is deemed necessary to get the patient thoroughly warm before op- eration, and to minimize shock in every way, the room being well heated and the table provided with a hot water bed. The writers advise operating these cases in the Trendel- enburg position. Just before begin- ning, subcutaneous saline administra- tion is started, and this is continued throughout the operation, 3 or 4 pints of fiuid being thus given. Hender- son's closed ether anesthesia is pre- ferred. Fraser and Bates (Brit. Med. Jour., Apr. 8, 1916). A pulseless patient never benefitij by operation. A total absence of pulse, however, must not be con- founded with an extremely rapid pulse, which perhaps cannot be counted. Such patients may be snatched from death by operation. A truly pulseless patient must be treated first and every effort made to bring back the arterial tension; while with a patient who still has a pulse no time should be lost in ligating large blood-vessels and removing pos- sible causes of sepsis. Operation within three hours has shown a su- periority over longer periods. Pa- tients with very little traumatic shock and otherwise in good condi- tion are practically certain to recover after very early intervention. Vaquez has shown that after ordinary lapa- rotomy, a blood-pressure of 140 may be lowered to 100. Operation on a patient with a tension below 100 is inevitably followed by death inside of twelve hours. Below 100, the lower the tension the worse the outlook. It should be 120 and upward before one can feel certain of recovery. Quenu (Bull. Med., Oct. 28, 1916). The eflficient treatment of gunshot wounds involves the 2 principles of antisepsis and osmosis. These 2 prin- ciples, according to the writer, are fulfilled by a combination of equal parts of ichthyol and glycerin whinh he has been using in various military and civil hospitals for nearly 3 years. It is particularly efficient in wounds that refuse to heal under classic measures. Duggan (Pract. June, 1918). If, after a careful examination of the enlarged wound, it is found that the peritoneum is not involved, the exposed tissues are carefully cleansed and the wound is closed, deep sutures being used to hold the tissues in ac- curate apposition. As already stated, the possibility of ventral hernia should be borne in mind : the patient should be kept in l)ed for some time ?.nd a bandage be worn until all local weakness has disappeared. If the lesion is intraperitoneal, a median incision of good size should always be used. The presence of gas indicates a lesion of the intestinal canal, requir- ing examination of the whole canal, with closure of each hole as it is reached. All drains should be removed at the end of 36 to 48 hours. The wounds should be closed with through and through sutures of silk- worm gut, as closure can thus be more rapidly done. The patient should be placed in the Fowler po- sition and proctoclysis immediately instituted. Morphine and atropine are prescribed as required. If undue vomiting occurs the stomach should be washed out No attempt to move the bowels should be made for 3 or 4 days. F. W. McGuire (N. Y. Med. Jour., Sept. 21, 1921). If, after a stab wound, the parietal peritoneum alone is found incised or penetrated and there is no evidence that the organs behind have suffered injury, the tissues must be cleansed with great care and the peritoneal flaps brought together, the serous surfaces being kept in contact. A continuous catgut suture is used for the peritoneum ; the muscles and skin ABDOMINAL INJURIES (LAPLACE). 147 are then united and the wound is wall of the stomach the tubular closed. The measures already out- wound is contracted and obstructed lined to prevent ventral hernia are sufficiently to prevent leakage until also indicated for the deeper wound, the canal on the peritoneal side When laparotomy becomes neces- becomes hermetically sealed by firm sary the incision should be made in a plastic adhesions which prevent ex- spot affording the operator the great- travasation during the time required est opportunity for a wide field of for the repair of the visceral wound, action, and should be sufficiently If in larger wounds of the stomach long. A\ hen performed for the arrest the same degree of occlusion can of dangerous hemorrhage, a long be accomplished by the simplest me- median incision will enable the sur- chanical means, then such a pro- geon to reach any organ with ease : cedure should take the place of the an important factor, for the missile or more time-consuming methods of su- blade inflicting the injury may have turing now in general use. This can traversed harmlessly between several be accomplished with the purse-string coils of intestine and have caused a suture. rent in the organ most remote from In gunshot injuries tlie defect in the point of entrance. Again, the the stomach-wall is circular and the incision should be free, so as to make wound-margins contused; hence the it possible to easily reach all parts of deep sutures could at first furnish a the abdomen to allow of a thorough barrier to the escape of stomach-con- removal of all extravasations which tents only for a short time, as their might otherwise ultimately cause hold in the necrosed tissues would complications. be imperfect and only of brief dura- As the late Nicholas Senn taught, tion. In short round wounds the cir- one of the important elements of sue- cular suture is the one which will cess in the treatment of gunshot and bring and hold together in permanent stab wounds of the stomach is time, uninterrupted contact the serous sur- Unnecessary time lost in finding and faces in the most efficient manner. In suturing the visceral wounds is a the treatment of gunshot wounds of source of immediate danger to life the stomach the principal object of which should be eliminated as far as suturing should be to close the per- possible by means which enable the foration in such a way as to guard surgeon to make a quick and correct securely against extravasation, and at diagnosis, and by resorting to a the same time approximate and hold method of suturing which closes the in apposition a maximum surface by wound safely and securely with the intact healthy peritoneum. This is least possible delay, and which leaves accomplished by making a cone of it in a condition most favorable for the injured part of the stomach with speedy definite healing. It is well the apex corresponding with the known that small penetrating wounds wound directed toward the lumen of of the stomach often heal without the organ. The purse-string suture operative intervention. By contrac- applied in the manner that will be tion and relative displacement of the described in the experimental part of different muscular lavers of the thick this section will maintain this cone 148 ABDOMINAL INJURIES (LAPLACE). until the healing- of the visceral with the purse-string suture in a few- wound has advanced sufficiently to moments. In doubtful cases inflation render further mechanical support of the stomach should invariably be superfluous. The cone on the mucous practised for the detection of a second side of the stomach acts in the manner and possibly a third perforation, of a valve, which in itself is an ef- The experiments demonstrated the fective barrier against the escape of safety of the circular suture in the stomach-contents, while the circular treatment of gunshot and other pene- suture constitutes almost an absolute trating wounds of the stomach. All safeguard against leakage, and brings of tlie animals operated upon in in contact the serous surfaces in the this manner recovered and the repair interior of the cone. For wounds of of the injuries as shown by the the posterior wall of the stomacli the specimens are ideal. The absence of author recommends a purse-string adhesions over the posterior wound suture of heavy durable catgut to be and tlieir constant presence over the applied through the anterior wound, anterior wound indicate that the The anterior wound is closed with a presence of the silk ligature and the purse-string suture of silk of medium needle punctures were the causes of size applied to the base of the cone on the circumscrilicd plastic peritonitis the serous side. It is desirable that which produced them. In none of the circular suture should cause no the specimens could any indications necrosis of the included tissues. By be found of necrosis of any of the using an absorbable suture in closing inverted tissues, and included in part the posterior wound in the interior of by the circular suture, the stomach this object is gained, as In the course of three weeks the only a small part of the thickness of continuity of the mucosa at the seat the stomach-wall is subjected to pres- of the injury was completely restored, sure, and the tension caused by the The result of these experiences has ligature is gradually lessened by sof- convinced the author that the circular tening of its material, and is entirely suture compares favorably with the removed by the absorption and diges- methods of suturing^ in general use, tion of the ligature in less than three and besides has the great advantages weeks. over them in the case of its applica- The wound of the posterior wall of tion and the saving of much valuable the stomach is found and made ac- time. cessible by inserting through the an- Suturing of the posterior wound terior wound a grasping forceps with by partial eversion of the stomach which the posterior wall is seized at through the anterior obviates un- a point where, from the course of the necessary handling of the organ and bullet, the second wound is supposed the necessity of interfering with the to be located. Through a wound vascular supply incident to exposure large enough to admit the index finger of the posterior wound, as is done by the greater part of the posterior wall the methods most generally practised, of the stomach can be made acces- If extravasation into the retrogas- sible to sight and touch, and the trie space has taken place, flushing perforation can be located and closed through the posterior wound and a ABDOMINAL INJURIES (LAPLACE). 149 vertical slit in the gastrocolic liga- ment and gauze drainage through the latter are invariably indicated. The stomach and the transverse colon are best brought to view by an incision through the rectus muscle. In the case of the stomach hernia of the mucous membrane will facilitate recognition of the lesion. The as- cending colon requires lateral incision on the right side, and the descending on the left. These also should be sufficiently long to facilitate the search for the injury or injuries that may be present in the organ itself and beyond. In cases seen later, when perito- nitis has already set in, a small supra- pubic incision for insertion of a tube to the bottom of the pelvis, with the Fowler position, will give the patient a chance of recover>'. Mayo-Robson (Brit. Med. Jour., Dec. 4, 1915). The incision may be such as to intersect the wound of entrance. This is desirable at all times, the aim being, of course, to always avoid un- necessary solutions of continuity. Such an incision can fortunately be made in manv of the cases in which the hemorrhage is not formidable. In abdominal cases where there is much blood, the authors quickly swab it away with a long- roll of dry gauze before examining the viscera. In early cases with extensive peritoneal soiling they wash out the peritoneal cavity; in later cases, and those with signs of peritonitis, they do not. Drainage by a sing'e Keith's tube passing into the pouch of Douglas proves sufficient : in special instances local or flank drainage is necessary. Eraser and Bates (Brit. Med. Jour., Apr. 8, 1916). Experience in 356 cases showed that for injuries of the small intes- tines either pursestring suture or re- section should be employed, the for- mer being given preference wherever possible. When resection is required end-to-end anastomosis seems to give better results than lateral and is m.ore rapid. Extravasated material is best removed by mopping with gauze wrung out of hot saline. Saline should never be used for lavage of the abdominal cavity. Lockwood, Kennedy, Macfie and Charles (Brit. Med. Jour., Mar. 10, 1917). No important change in the tech- nique of operation in gunshot wounds of the abdomen was introduced dur- ing the war, except that it became the rule to close without drainage. A drain often leads to infection. Fre- quently all laj^ers of the abdominal wall were closed but the skin, as late infections often resulted from the latter. If a drain is used at all, it should be a loose gauze drain. The mortality in gunshot abdominal wounds was extremely high," but this mortality occurred largely on the field as a result of hemorrhage and shock. J. H. Gibbon (N. Y. Med. Jour., June 28, 1919). Hemorrhage. — When the abdom- inal cavity is opened and the hemor- rhage, which is usually more venoits than arterial, is marked, the blood rapidly accumulates in the most de- pressed portion of the cavity from an invisible source. To mop out the blood with sponges is generally rec- ommended ; but such a procedure does not cause the hemorrhage to cease, — the first desideratum. In these formi- dable cases an assistant should at once introduce his hand through the wound — hence the advisability^ of a long incision — and compress the ab- dominal aorta below the diaphragm. This procedure immediately checks the flow. If any difficulty is experienced, the digital pressure upon the aorta may, for an instant, be decreased, and a sudden gush will point to at least the direction from which the blood comes. 150 ABDOMINAL INJURIES (LAPLACE). The necessary steps are then taken to arrest the flow, and the abdominal aorta is released as soon as possible, —not suddenly, but by a gradual re- duction of pressure. The measures to be employed in arresting- hemorrhage var\^ according to the organ involved. Gunshot wounds of the liver are frequently stellate, and rents, radiating from the bullet-track in various directions, greatly increase the bleeding surface, the parenchyma in this organ taking part to a great degree in the emission of l)lood. To force resilient sponges into tlicse tears is to increase their depth. If the wound be not ver>' ex- tensive, it may be sutured with catgut or cauterized with the actual cautery. If the wound is extensive it had better be packed with long strips of iodo- form gauze, one end of which is brought out of the external wound. Of 5 cases in which projectiles were extracted from the Hver. In only 1 was the projectile removed immediately after the injury. In the other four it had remained in the liver for from 10 to Zi months. In all cases the extraction was done under the control of the radioscopic screen. In but 1 instance was the opera- tion indicated by the symptoms of secondary infection; in the others the indication was furnished by the pain caused by the projectile. In 1 case the extraction was done by the lumbar route; in the others, by laparotomy. The incision in the liver varied from 1 to 3 cm. in length according to the size of the projectile. The pro- jectile was removed with the forceps. In no case was there any extensive hemorrhage, but in 1 instance a pyo- pneumothorax developed, following the operation. L. Sauve (Bull, et mem. de la Soc. de Chir. de Paris, xlv, 1461, 1919). The spleen is next in order as to profuseness of hemorrhage. The same procedures may be adopted as for the liver, but the introduction of iodoform strips is to be preferred. If these means fail, splenectomy is the onlv measure left. -Sometimes a portion of the organ projects through the wound; removal of the protruding portion should be practised after passing a ligature around the mass. The walls of the stomach and intes- tines may also give rise to marked hemorrhage notwithstanding their comparative thinness. The numi)er of vessels coursing through them, however, is very great. in these cases it is best to hem the margins of the wounds with fine silk. The bladder may be treated in the same way. The mesentery sometimes bleeds profusely when perforated. The mesenteric vessels should be ligated en masse with fine silk. Blood escaping through bullet holes in the bowel gradually works its way downward into the small pelvis and is not absorbed. Often an abscess forms, and later walling-off adhesions are broken down and secondary peritonitis results, usually extremely serious. There are two ways to render harmless the infected extravasated blood: (1) When the patient is seen in the first twenty- four or forty-eight hours a very small laparotomy incision is made above the symphysis (under local anesthesia) just large enough for a rubber drain the size of the finger, to be carried down into the small pelvis. The patient keeps in a half- sitting position or lies on his side. (2) When not seen until later, the space between the rectum and the bladder must be carefully examined through the rectum. If there is any tenderness, protrusion, tenesmus or ABDOMINAL INJURIES (LAPLACE). 151 difficulty in micturition, the region is opened up at once. Payr (Mimch. med. Woch., Aug. 18, 1914). Report of the case of a man who had received 2 stab wounds, 1 through the costal cartilage of the left side and 1 in the right thigh. At operation the peritoneal cavity was found full of blood, and an incised wound on the stomach was bleeding. This was closed by a double row ot Lambert sutures. Shock, secondary anemia, and collapse followed, and the patient continued to vomit blood, also developed evidences of pneu- monia. Bayliss's gum acacia solution and blood transfusion, however, turned the tide, and he ultimately re- covered. C. W. Bowie (Jour. Royal Army Med. Corps, Apr., 1921) Hemorrhage of the kidney is ar- rested in the majority of cases by iodoform-gauze package. If this should prove ineflfectual the organ must be exposed and the vessels tied if possible. If not, nephrotomy or nephrectomy should be resorted to. The latter operation does away with the chances of complication attending the former, while the kidney of the other side assumes the function of both. For extraperitoneal injuries of the anterior aspect of the bladder, if high and if after regularization they can be correctly sutured, the practice should be suture with a permanent catheter. If the lesion is in the vicin- ity of the neck, suture should not be tried. The practice should be cystos- tomy as high as possible and a cath- eter placed after an interval. For intraperitoneal injuries, if in the apex or the posterior aspect, resection of the margins is indicated, suturing in two places with fine catgut, and a permanent catheter. The Douglas sac should be closed by a row of sutures, thus isolating the wound from the rest of the abdominal cavity, to be followed by cystostomy. As wounds of the fundus are usually produced by perineal projectiles, they necessitate a lateral perineotomy or even a transverse, made as wide as possible so that a loose tamponade in contact with the bladder wall may be instituted. H. Erin (Bull, et mem. Soc. de Chir. de Paris, xliii, 1086, 1917). Of 43 bladder wounds met with since the beginning of the war, 6 ran a benign course. Such are usually bullet wounds; shell wounds show marked tears and easil}^ produce a septic condition. In 15 cases there was a vesico-intestinal fistula, with 12 spontaneous recoveries without oper- ations in a period varying from a few weeks to four months. Lesions of the pelvic girdle were observed in 29 cases. A foreign body required re- moval in 12 cases. Treatment should be immediate and include disinfection of the tract, removal of fragments of bone, etc., and extraction of foreign bodies. The. cavity should be thor- oughly explored both by radiography and radioscopy-; if these are not avail- able, every other known method of surgical exploration should be uti- lized. It seems necessary as soon as possible, sometimes on the first day, to make a suprapubic cystostomy. The indwelling catheter in such cases is only a makeshift. In all cases where an early operation was done, recovery followed; but, even when done later, drainage was good and cicatrization was hastened. F. Le- gueu (J. d'urol. med. et chin, Paris, vii, I, 1917). War wounds of the bladder are grave, but surgery and the retention catheter generally bring the men through. All of 29 patients recovered except 3, 2 succumbing to their ex- tensive wounds and 1 dying later from tetanus. Immediate suprapubic cystostomy is necessary when the wound has involved the peritoneum or rectum or both, and when the an- terior wall has been perforated. With a wound in the lower part of the bladder, drainage perfect, there is no need for immediate cystostomy unless fever and retention call for it. 152 ABDOMINAL IN7URIES (LAPLACE). Under other conditions the author prefers cystotomy; he deprecates fur- ther any attempt to suture the blad- der wall at once unless the wound is intraperitoneal. Cathlin (Lyon chir., Jan.-Feb., 1918). Perforation. — The fact that the in- testines are, at times, perforated in twenty spots by a bullet sug-g-ests the considerable degree of care that should be given to this part of the procedure, which is carried out in the following- way: The perforation nearest the rectum having- been de- tected, the portion of intestine per- forated is gently brought into full view. An assistant causes the gas in the portion of gut below the lacera- tion to escape through the latter by slight pressure. This being done, the next step is to ascertain whether there is another perforation above. A fresh, aseptic glass tube is placed at the end of the insufllating tube and introduced into the wound witii the tip directed away from tiic rectum^ The assistant now being directed to comjiress the intestine below the per- foration, a small amount of gas blown above the latter will inflate the upper segment if there is no opening, or indicate the location of the perfora- tion if there is one. As soon as the latter is detected, the tube is with- drawn, the neighboring intestine on each side of the first perforation is disinfected, and the opening is closed. This procedure is renewed until all perforations have been found and closed. This general plan renders unneces- sary the removal of the intestines from the abdominal cavity during any part of the operation, the source of complications in many cases, and of death bv aggravated shock in others. Penetrating abdominal wounds made by rifle bullets are very deceiv- ing. Many of these patients are brought in apparently in very good condition; they are able to walk and are not in pain. If nothing is done for them, often within twenty-four hours, they will have developed gen- eral peritonitis from a small leakage in the intestinal tract, and they can- not then be saved by any method. These patients should be subjected to operation at once if the wound is clearly penetrating, and many times a perforation is found where least ex- pected from the symptoms. The dis- tended stomach may have a perfor- ating wound within its walls and should be carefully explored in all such cases. Patients having wounds of the liver usually recover unless there is too much destruction of tis- sue. Bleeding from these wounds is controlled by gauze packs. If it is difficult to control bleeding from the spleen, or if this organ is badly trau- matized, splenectomy seems prefer- able to an attempt to repair. In wounds of the intestine, it seems much safer to repair the wound whenever possible rather than resect the intestine. Penetrating wounds of the intestine, unless operated on early, have given a very high mor- tality. E. S. Judd (Journal-Lancet, Nov. 1, 1918). The manner of closing the wound is that indicated for lacerations fol- lowing blows. The stomach and in- testinal perforations being treated in the same way, the margins of the w^ound are turned inward and the serous surfaces are united by a con- tinuous, fine-silk Lembert suture or by interrupted sutures, including the serous and muscular coats and the submucosa. These are cut short and left in, being eventually discharged per attum. In simple suture of the small gut the wound must be small, with edges undamaged and mesentery intact. ABDOMINAL INJURIES (LAPLACE). 153 Wounds by bomb fragments are ideal for suture. The wound edges were not excised, and linen thread was em- ployed. Resection and anastomosis are indicated in the event of many perforations, extensive injuries, and mesenteric involvement. Eraser and Bates (Brit. Med. Jour.. Apr. 8. 1916). Small round perforations may be closed with a single purse-string suture of silk or linen. In larger ragged wounds, a running suture is efficient in securing accurate closure of the serosa over the defect. In extensive tangential lacerations, ap- plication of the running Lembert suture should be preceded by closure of the wound with a simple running suture traversing the entire thickness of the gut wall. In wounds at the mesenteric border, care must be taken that the perforation in the muscular coat of the intestine itself is closed. After turning in the mus- cularis and mucosa of the gut at the site of perforation with Lembert su- tures, the opening in the mesentery is closed with a simple running su- ture. Complete division of the gut requires circular suture anastomosis or invagination of the ends with lateral anastomosis. The latter is the safer and amounts eventually to cir- cular suture since the gut at the junction straightens out and assumes a nearly normal conformation. J. R. Eastman (Jour. Ind. State Med. Assoc, Nov., 1917). Discussing thoraco-abdominal in- juries involving penetration of the diaphragm, with damage to subjacent viscera, the writer states that the re- pair of injuries to the diaphragm should be immediately carried out or else the diaphragmatic injury is en- larged so as to deal with intra- abdominal complications. There are well-defined limits to the amount of work that can be performed upon the viscera of the upper abdomen, for with reduction of herniated viscera and repair of injuries to the liver, spleen, portions of the cardiac end of the stomach, and occasionally the colon, very little further operative manipulation can be carried out. For injuries lower down in the abdomen it is necessary to supplement the thoracic technique with a laparotomy. Suturing of the diaphragm is com- paratively simple, and after the first suture is tied it is utilized as a trac- tion suture, and the remaining por- tion of the diaphragm readily sutured with a lock-stitch of No. 2 chromic catgut. C. G. Heyd (Trans. Amer. Assoc. Thoracic Surg.; Med. Rec, Apr. 16, 1921). At times the tissues around a per- foration are sufficiently contused to r.ender an otnental graft necessary. Enterectomy is sometimes required, and not infrequently exsections of the intestine are necessar\'. In that case the intervening- portion, if it is not too long, had better be resected, thus avoiding a double operation in the continuitv of the gut. After the active measures described have been carried out the extravasa- tion of the contents, of the stomach or intestines may make it necessary to flush the peritoneal cavity. Warm, sterilized water should be used, but care should be taken not to handle the intestines roughly. By turning the patient on his side the fluid is poured out. The abdominal cavity is then dried with large sponges wrung out of warm, sterilized water. Chill- ing of the viscera should be carefullv avoided, and the parts should be exposed to the air as short a time as possible. Drainage is sometimes necessary, especially for wounds of the solid viscera, such as the liver, spleen, kidneys, etc., in which active meas- ures were not resorted to early. The weight of evidence, however, stands in favor of dispensing with drainage whenever it is possible. In bad in- fection large drainage tubes may be 154 ABORTION (WRIGHT). inserted into the flanks as well as the pelvis. Twenty-five cases of recto-colic rupture due to compressed air were collected by the writer. The symp- toms are those due to intestinal rup- ture and shock. Of the 16 cases operated on, life was saved in 7, in- cluding the author's 2 cases. The operative mortality is therefore 57 per cent. When the intestinal perforations are multiple, as is usually the case, and when the intestine is reduced to its mucosal coat alone, suture is useless. If the condition of the patient is poor, the intestine should be brought to the surface and fixed to tlic ab- dominal wall to form an artificial anus. If this is not possible, an enterectomy with a colo-colic or colo-rectal anastomosis is indicated. In the writer's cases such anastomo- sis was impossible because of the condition of the rectum. The upper stump of the colon was therefore fixed to the al)dominal wall as a per- manent artificial anus. Both patients made good recoveries. G. Jean (Presse med., xxix, 675, 1921). To summarize : we will say that immediate exploration of the abdom- inal cavity is indicated as soon as it is suspected to have been penetrated or in any way injured by a trauma- tism. The injury to its contents must then be repaired under strict aseptic precautions. Should no lesion be found, the mere exploration should result in no serious damage. After-treatment. — Food should be withheld for thirty-six hours, but a little water and brandy, in teaspoon- ful doses, may be allowed, especially if there is any degree of shock. In that case it is advisable also to use stimulants by the rectum or sub- cutaneously. Nutritive enemata of beef-tea and milk are necessary to sustain the patient's powers. Proctoclysis of normal salt solu- tion according to the Murphy gradual method should be resorted to. The head of the bed should be raised to apply the Fowler principle favoring the gathering of secretions in the pelvis, where the absorption is less rapid. During this procedure no food should be given by the mouth. If the patient is weak, rectal alimenta- tion is indicated. In the less severe cases liquid food may be permitted by the evening of the second day. and soft, easily digested food after a week, rectal alimentation being continued until then. The sutures can be removed on the ninth day. The closure of the external wound must be coini)lete before the patient can be allowed to leave his bed, and the danger of a ventral hernia should be counter- acted by means of an abdominal supporter. Hypodermic injections of strych- nine, Yqq to Yso grain, three times a day, according to indications, will prove most effectual in maintaining the strength of the patient and toning the muscular wall of the intestine. Ernest Lapl.\ce. Philadelphia. ABORTION.— DEFINITION. — Abortion is the expulsion or removal of the fructified ovum before the fe- tus is viable, — meaning by the term "viable" that the fetus has reached such a stage of development that it can live, thrive and grow after birth. We cannot say definitely when the fetus reaches that stage, but it has been the custom to consider that it ABORTION (WRIGHT). 155 becomes viable at the end of the seventh lunar month or the twenty- eighth week of pregnancy. Still, a very young fetus may breathe after delivery. This occurred, for ex- ample in 3 cases (2 in the fifteenth and 1 in the nineteenth weeks, re- spectively) reported by Glockner. In the first of these there were six re- spiratory movements before and five after severing- the cord, the fetus living one hour. In the second case the fetus lived an hour and a half and breathed five times. The third fetus lived but half an hour and breathed eight times. The autopsy showed air in the stomach, but the lungs were empty. From a clinical standpoint, how- ever, the fetus is not viable before the end of the seventh calendar month. Premature labor or delivery means the termination of pregnancy between the end of the seventh month and full term. In certain cases it is difficult to distinguish between late abortion and early premature labor. As to the time of occurrence, -it has seemed convenient to consider two varieties : early abortion, when it occurs before or about the end of the third month of pregnancy, and late abortion, when it occurs between the latter part of the third month and the end of the seventh month of preg- nancy. Three varieties as to the methods of occurrence are also recognized : the spontaneous, when the abortion occurs without any outside interfer- ence, and is caused by some abnormal condition of the mother or fetus ; the accidental, when the abortion is due to accident ; and the induced, when the abortion is produced artificially by interference from outside. Induced abortion is deemed legitimate when it is produced by a physician for just cause. The cause is considered just only when the abortion is induced to save the mother's life which otherwise is imperiled. When the abortion is induced without such just cause, that is, when it is done for improper or immoral reasons, whether by the mother or the professional abortionist, it is known both from a medical and legal standpoint as criminal abortion. In the author's clinic during the past 6 years, in a total of 5500 cases, he has had to perform abortion only 31 times. Again, although 134 women came to the clinic for therapeutic abortion as follows: (1) of their own accord, 55; (2) sent by physicians, 72; (3) sent from the intern clinic, 4; (4) sent from the obstetric dept. 3, only 30 had to be operated upon. The author holds that at least two- thirds of the therapeutic abortions performed by private physicians are not indicated and are unnecessary when the cases are dealt with by skilled obstetricians. This is the evil practice that must be suppressed. On no account should therapeutic abortion be included among legiti- mate obstetrical operations. There is scarcely any agreement among competent physicians as to the causes which are strictly indica- tive of induced abortion. In every case where an abortion is considered a consultation should be held with a special internist who would not be concerned with the pregnancy but with the absolute condition of the woman as to concomitant disease. The author recognizes that 80 per cent, of abortions have their initiative from the woman herself. G. Winter (Zeit. f. Gynak.,Jan. 6, 1917). Criminal abortion, according to the writer, a professor in the university law department, should be classed with espionage, counterfeiting, an- archy, etc., as the crime against society is more important than the 156 ABORTION (WRIGHT). individual character of the crime. The birth-control propaganda should be suppressed, as the arguments in favor of birth control apply also to voluntarj' abortion. Criminal abor- tion cases should not be given a jury trial, as the jurj'men do not realize the social danger of the crime, and they yield to intimidation by the abortionists, usually powerful and always with a protecting backing. Another point which he emphasizes is that a physician cited in a suit for criminal abortion should be relieved of the ban of professional secrecy, so that his testimony can be used against the abortionists. Berthelemy (Bull, de I'Acad. de Med., Paris, Sept. 4, 1917). The writer deprecates the modern tendency to enlarge the indications for induced abortion. The medical indications have still more been rein- forced by social and economic con- sideration, without speaking of the pressure brought to bear on the medical man by the patient's relatives when pregnancies are too frequent. Of 202 cases sent to his clinic for therapeutic al)ortion, only 59 were performed there in the lapse of 5 years. The reason for this condition of affairs is due to a change in ethical ideas in Germany. Bumm (Berl. klin. Woch., Jan. 7. 1918). As to frequency, it is impossible to estimate even approximately the pro- portion of preg^nancies terminating- in spontaneous abortions. Women who object to having large families have such a multitude of expedients to cut short their pregnancies, and fre- quently conceal their methods so carefully, that our estimates as to percentages cannot be exact. From the results of our experience in private practice it is indicated that abortion occurs from accident or spontaneously in 1 out of 10 pregnancies, that is. 10 per cent. However, if we include induced abortions (legitimate and criminal), it is probable that abortion occurs in 3 out of 10 pregnancies, that is, in 30 per cent. The figures of the Paris Maternite from 1897 to 1905, as collected by G. Rimette, show 9875 pregnancies, 1457 abortions, 627 spontaneous abortions, 414 complicated abortions, 367 in- fected abortions, and 27 deaths from abortion. MichailofY, who bases his figures on 257,988 births in one of the Russian maternities, found that the proportion of abortions to full-term deliveries was about 1 to 10. Keyssner, in his polyclinic material, found 469 abor- tions to 2623 confinements, or 1 to 5.6. Miscarriage. — We consider abortion and miscarriage are synonymous terms. In former times the terms were not considered so, nor are they now in some quarters. Many, if not all, of the Rotunda men, and some obstetricians of Xorth America, still use the term miscarriage in the old- fashioned way. According to them, miscarriage is a term applied to the expulsion of the ovum between the beginning of the fourth and the end of the seventh month, that is, between the time of the complete formation of the placenta and the time that the fetus becomes viable. Those who thus define miscarriage say that abor- tion is the term applied to the expul- sion of the ovum before the end of the third month, that is, before the forma- tion of the placenta has been fully completed. SYMPTOMS.— The symptoms of abortion are hemorrhage, a brown discharge after the death of the ovum, pains in the pelvis, complete or partial dilatation of the as uteri, expulsion of the whole or part of the ovum. ABORTION (WRIGHT). 157 The hemorrhag"e in the majority of abortions is not profuse, and may continue a long time. In a certain class of cases, however, the hemor- rhage is very profuse and sometimes causes death. Some obstetricians think that hemor- rhage in early abortion is never pro- fuse enough to cause death. Cer- tainly the hemorrhage before the formation of the placenta is seldom dangerous to life. There are excep- tions to this rule, however; but, so far as we know, the majority of the fatalities from hemorrhage in early abortion occur in cases of criminal abortion where sharp or pointed in- struments are used. In considering the symptomatology of abortion, however, it is ver}^ im- portant to obtain a clear conception of the two varieties commonly recog- nized, viz. : the "threatened" and the "inevitable." [The importance of this distinction as- serts itself in connection with treatment. In the case of threatened abortion we are in doubt as to whether the uterus will be emptied or not, and our treatment aims at controlling the influences which are pro- ducing the symptoms of abortion, such as hemorrhage and uterine contractions. In the case of inevitable abortion the con- tents of the uterus will be held or partially expelled by nature's efforts, and we pursue a line of treatment entirely different from that adopted for threatened abortion. Our aim now is to assist nature in expel- ling the contents of the uterus as soon as possible with safety to the mother. A. H. Wright.] The symptoms of threatened abor- tion are hemorrhage, pelvic pain and perhaps a slight dilatation of the os, especially in multiparae. The hemor- rhage, as already mentioned, is com- paratively slight in a large proportion of cases, and may continue for nine or ten weeks or longer without ending in actual abortion. The pains which are caused by uterine contractions may be fairly severe and may con- tinue for some time without causing the expulsion of the ovum. In inevitable abortion there are also hemorrhage, pelvic pains and more or less dilatation of the os, but these phenomena are more severe and pro- nounced. It is sometimes, in fact, very difificult to decide when an abor- tion becomes inevitable. Probably the safest guide is the hemorrhage. If the fetus is dead, or if the mem- branes are ruptured, abortion is also deemed inevitable. No definite line of demarcation can be established in this regard. The symptomatology of abortion varies, of course, to a certain extent according to the time at which it occurs. As carefully collated by Lu- taud, of Paris, the symptoms at the different periods are briefly as fol- lows : — Abortion During the First Month. — This usually gives rise to symptoms simulating those of retarded menstru- ation. Slight pains in the back in the region of the uterus are complained of; the symptoms, in this particular, resemble those of normal labor, but are very much less marked. Blood, blood-clots, and flakes of the mucous membrane of the uterus are gradually expelled during several days. The ovum is expelled entire, but it is so small that it is discovered, as a rule, with great difficulty. Abot^ion During the Second Month, — Inasmuch as the uterus has de- cidedly increased in size as compared with its size in the first month, the contractions and pains are compara- tively stronger. The embryo is usu- ally expelled inclosed in the unbroken 158 ABORTION (WRIGHT). membranes. Sometimes, however, the latter are ruptured. The embryo and membranes may be detached from the uterus in two ways : — (a) By hemorrhage between the membranes and the uterus, followed by uterine contraction. (b) Ey contraction of the uterus, followed by hemorrhage. In the lat- ter case the abortion is more pro- longed, the membranes being de- tached but slowly from the uterus. If the embryo be still living, the abortion lasts longer, and the hemor- rhage is greater. If the embryo be dead, the whole is usually expelled like a foreign body, and without rup- ture of the membranes. Examination of the uterus will show that it is increased in volume and situated lower down in the pelvis than normally. The cervix is dilated, softened, and filled with blood-clots. The dilatation is more marked in multiparse than in primipar?e. The cervix, though dilated, does not become efifaced, and the embryo contained in the unruptured mem- branes may pass through the cervix and be expelled. If the membranes are ruptured, however, the embryo passes by itself, the very thin umbili- cal cord breaks, and the cervix closes. The membranes are, in this latter case, expelled later on. The mem- branes are ruptured about once in every 2 cases. Abortion from the Beginning of the Third to the End of the Fourth Month. — This occurs nearly always in two stages, the first consisting in the expulsion of the fetus, and the second in the expulsion of the membranes and placenta. The cervix in this form of abortion tends to diminish in length. The uterine contractions act more power- fully than in the previous forms of abortion. Under their influence the membranes are ruptured and the fetus is expelled. The placenta may still be adherent ; the cervix then closes again, and the placenta and membranes are ex- pelled later on. Hemorrhage is likely to accompany the delivery of the placenta and membranes, especially when the former is only partly de- tached. Under these circumstances each uterine contraction is accompa- nied by hemorrhage. The placenta may be already de- tached when the fetus is expelled ; in such a case it is likely to be expelled immediately after the latter, before the cervix closes, but part of the decidua may remain in the uterus after delivery of the placenta. This occurs most frequently when the fetus is dead. Statistics show that retention of the placenta occurs most frequently dur- ing this period. Abortion During the Fifth and Sixth Months. — The fetus and pla- centa are almost always expelled sep- arately. Uterine contraction is more marked ; the cervix tends to become more effaced and to dilate. Delivery of the placenta usually fol- lows delivery of the fetus rapidly, and the tendency to hemorrhage is less marked than in the previous forms of abortion. Of 501 cases of abortion analyzed by Varnier and Brion, the fetus, or embryo, and the placenta were ex- pelled separately in 453, and together in 48 cases. When the delivery oc- curred in two stages, the time found to elapse between the expulsion of the ABORTION (WRIGHT), 159 fetus and that of the placenta was as follows: 120 cases, within 15 min- utes; 81 cases, from 15 to 30 minutes; 78 cases, from 30 to 60 minutes ; 83 cases, from 1 to 4 hours. Whenever the placenta and mem- branes are not expelled within four hours after the expulsion of the fetus, or embryo, there is retention of the membranes and placenta. Abortion may take place suddenly, or resemble, in that particular, the irregular periodicity of normal labor, with more or less hemorrhage. It may, indeed, last several days, owing" to weakness of the uterine contrac- tions or adhesions to the uterus or retention in the cervix of the masses to be expelled. (Rokitansky, Schii- lein.) Sudden or rapid abortion is frequent during the first two months ; when the expulsion takes place after the third month it generally presents tlie characters of normal delivery. The menstruation returns earlier after abortion than after a normal labor. Englander, in a recent (1906) study of 57 cases of abortion, under- taken to ascertain the period of their first subsequent menstruation, found that in 64.9 per cent, the menses re- appeared in four weeks ; in five weeks in 14 per cent. The remainder varied, 1 patient going as long as six weeks after the abortion before menstru- ating. After labor, it is usually six to eight weeks before patients men- struate. DANGERS.— Just as parturition may be attended by deviations from the normal, so may abortion. Retention of the placenta occurs fre- quently. The latter is sometimes ex- pelled safely after some days, either entire or in pieces, but prolonged re- tention exposes the patient to hemor- rhage, toxemia, and septicemia. When completely detached, though retained, the placenta gives rise to no hemor- rhage, but if only partially detached such is not the case and copious hem- orrhage may thus l)e produced. In 15,000 cases of abortion studied by Seegert, fever occurred in 15 per cent. Of 633 patients, 182 had chills before they came under active treat- ment. Among the 15,000 patients were 450 who were severely infected ; of these 94 died. In 82 cases autopsy was made. Those cases showed the most severe symptoms in which the longest time elapsed before the uterus was completely emptied. Fever often ceased when the uterine contents were expelled. The general symptoms that follow hemorrhage (a weak pulse, vertigo, fainting, etc.) occur only when the loss of blood has been severe. Under these conditions septicemia, as evidenced by fetid lochia, chills, and high tempera- ture, is a probable complication. En- dometritis, salpingitis, and peritonitis have also been witnessed under such conditions. Tetanus is also another possible complication of these cases. Sterility commonly follows induced abortion. The writer observed 8 cases of sterilization, the result of induced abortions. All the women were mar- ried, in good health and none over 35 years of age. In each instance the abortion was induced soon after the first period had been missed, usually the second or third week. The abor- tions induced in these women were as follows: 3 had been relieved 5 times in 2 years; 2 six times in lYi years; 1 woman 9 times in 3 years; 1 woman 11 times in 5 years; 1 woman 14 times in 5 years. In later years when these women desired to 160 ABORTION (WRIGHT). have children they found themselves sterile. They cheerfully submitted to treatments which buoyed them with hopes from month to month, only to find that at the end of their course of treatment they were just as sterile as they were before they consulted the gynecolog-ist. Reder (Trans. Amer. Assoc, of Obstet. and Gynec. ; N. Y. Med. Jour., Nov. 23. 1918V ETIOLOGY AND PATHOGEN- ESIS.— There has been much theoriz- ing as to the causes of abortion, and in many instances, the exphmations and complicated classifications vouch- safed have obscured the subject in- stead of elucidating^ it. In a study of 164 instances of abortion, out of 563 patients exam- ined, the writer found that more than 20 per cent, probably over 25 per cent., were induced. Sixty per cent, of all induced abortions result in more or less permanent sterility. These are worst when caused by the midwife, the patient herself, and last by the physician. A positive Wasser- mann is obtainable in about 25 per cent, of all women who have aborted. Less than one-third of these give any history or show any physical signs of the disease. Syphilis interrupts pregnancy at any and all periods of gestation, and in more than 60 per cent, of pregnancies. Renal defi- ciency does it only in the event of renal decompensation at any period of gestation. G. D. Royston (Amer. Jour, of Obstet. Oct., 1917). It is generally recognized that the causes may be of maternal, paternal, and fetal origin.. The causes of abortion may be classified as follows: 1. Criminal provocation, direct or indirect. 2. Maternal, such as constitutional dis- ease, pelvic disorders, affections of the nervous system, etc. 3. Paternal, such as certain constitutional dis- eases, chief of which is syphilis, and old age. 4. Fetal, such as death of the fetus and diseases of the placenta. It is generally supposed that 50 per cent, of abortions are criminally pro- voked. Titus found 82 per cent, of a series of criminal abortions at the Johns Hopkins Clinic were incom- plete, and 78 per cent, of this same series were infected, streptococcus in- fections occurring in 34.3 per cent, of these cases. Under the maternal, paternal and fetal causes of al)ortion. syphilis is the most frequent cause. In 657 syphilitic women there were 35 per cent, of aljortions. Decidual endometritis is a cause of abortion in 52 per cent, of infected and 68 per cent, of uninfected cases, while retroposition is a cause in 30 per cent, of the cases. Lacerations of the cervix and pelvic floor account for 14 per cent, of all abortions. Can- cer and intra-uterine tumors are fre- quent causes. Poisons in the mater- nal blood from fevers such as small- pox, scarlet fever, typhoid and the like, are frequent causes of abortion, as are affections of the nervous sys- tem, as chorea, epilepsy and shock. Epidemic abortions caused by the bacillus abortus of Rang and strepto- cocci have been reported. The causes referable to the fetus include all the many diseases of the placenta, death of the fetus, and syphilis. The paternal causes include mainly syphilis, gonorrhea, albumin- uria, lead poisoning, and old age. J. E. Davis (Jour. Mich. State Med. Soc. xvii. 2. 1918). Maternal Causes. — Most cases of abortion are generally attributed to traumatisms, falls, blows — a cause not infrequently met with in the slums — the likelihood of premature delivery being decreased in proportion as the blow or other injury is remote from the region of the uterus. Operations, even sometimes when insignificant, have produced abortion. The so- called "aborting habit" is also recog- nized as a potent factor in this con- nection ; but this expression doubtless ABORTION (WRIGHT). 161 covers, in most instances, some hid- den and probably removable cause. The predominating" cause, however, according to statistics, is syphilis, to which are attributed over one-fourth of the cases. When it is contracted before conception, abortion occurs re- peatedly— early when the infection is of recent date, but gradually nearer term as the contamination is more remote. There comes a time, there- fore, when normal deliver}^ becomes possible. The prevailing view that syphilis is a prominent factor in the causation of abortion has been denied by Tren- chese and others. In a summary of 679 cases of abortion at the Michael Reese Hospital the writer also found that syphilis was an etiological factor in but 4 per cent, of abortions. Lack- ner (Surg., Gynec. and Obstet., xx, 537, 1915). In a study of the causes of abor- tion 563 patients were examined. A history of abortion was elicited in 178. The 164 selected for detailed study gave a grand total of 664 preg- nancies, 348 of which ended in abor- tion. Criminal abortion was the most common factor in the series; 51 out of 164 women having con- fessed to an induced labor, many re- peatedly. These 51 women had in all 220 pregnancies of which more than half, namely 118 (52.4 per cent.) resulted in abortion. Of these 118, 84 (71.1 per cent.) were frankly acknowledged to have been induced. Comparing the percentage of induced abortions with the abortions in his entire material, the writer arrived at the figure 23.8 per cent. Only 20 (39.2 per cent.) produced living chil- dren after having had abortions in- duced. Only 10 out of the 51 pa- tients had normal genital organs; the remaining 41 were more or less per- manently disabled. Among the 164 cases, 46 gave a positive Wassermann and 5 patients with definite histories gave negative reactions after having been treated. The writer holds that abortions are caused by syphilis much more frequently than the medi- cal public realizes. Royston (.^mer. Jour, of Obstet., Oct.. 1917). Next in order are malpositions and inflatnmatory disorders and tumors of the uterus and its adnexa, including ovarian cysts. Laceration of the cer- vix has recently attracted attention as a cause of abortion. The tear may be limited to the cervix, or it may extend upward to the body of the organ ; or again the rupture may occur above the external os. Charpentier refers to three distinct local uterine conditions in otherwise healthy women: 1. Ill-developed uter- us ; the muscular coat does not read- ily soften, yet remains very irritable. Rare. 2. Displacements, especially flexions. Spur at the angle of flexion hypertrophies interferes with uterine development. 3. Congestion of the body and cervix, due to idiosyncrasies. Endometritis. Debilitating influences of various kinds, such as insufficient food, ex- cessive physical labor or fatigue, men- tal and physical shock, the abuse of alcohol, tobacco (women employed in cigar, cigarette, etc., factories), car- bonic oxide (as shown by the frequent occurrence of abortion in cooks) and lead, including paternal intoxication by this metal, tend also to bring on miscarriage. Great shock or injury is sometimes bet- ter borne by pregnant women than fre- quently repeated shock, e.g., the use of the sewing machine with the foot. Davis has reported cases illustrating the fact that motoring during the early months of pregnancy is frequently followed by abortion. The danger seems to lie in the fact that the rapid motion of a motor car subjects the patient to many small, fre- quent jars. The characteristic of abortion 1—11 162 ABORTION (WRIGHT). following motoring is its slow and in- sidious development without bright hemor- rhage or pain. These abortions are, as a rule, incomplete, and require curetting. While motoring is dangerous in early pregnancy, in the later months of gesta- tion and with reasonable precautions as to smoothness of roads and moderation of speed it may prove exceedingly useful. Editoks. Debilitating- diseases have also been found to induce it. Influenza, in which the general adynamia is marked, has been recorded as a cause. In Asiatic cholera, abortion is almost invariably produced. The view that Bacillus abortus (Bang) is pathogenic for human be- ings is not proven, although it is pos- sible to cause antibodies for Bacillus abortus to appear in the blood-serum of adults by feeding a milk which is naturally infected with Bacillus abor- tus and which contains the Bacillus abortus antibodies. Cooledge (Jour. Med. Research, July, 1916). The writer found that complement fixation reactions with the polyvalent antigens of bacillus abortus (Bang) and bacillus abortivo-equinus and the sera of SO women aljorting in the early months of pregnancy yielded negative results. Williams and Kol- mer (Am. Jour, of Obstet.. vol. Ixxv, p. 194, 1917). A bacillus has been incriminated by Bang as a cause of abortion, but it is not receiving much support. Conversely, conditions which tend to exaggerate the contractility of the uterine muscle are also recognized causes. Ergot, copper sulphate and other "abortifacients" are familiar agents of this class. This evil action has also been attributed to quinine, but tiiere is reason to believe that this valuable remedy should not be with- held in pregnant woiuen, when in- dicated therapeutically, especially in view of the fact that malaria itself tends to cause abortion. Thus, in a study of the action of quinine on pregnant women, Frederici found that in 49 pregnancies quinine had been used in 47, the patients suffering more or less severely from malarial fever; 47 terminated at the usual period by the birth of a chlid, and 2 aborted. In these 2 cases he deems it extremely probable that the high fever from which they suffered was instrumental in producing abortion. He concluded that medicinal doses of quinine were powerless to induce abortion. The writer collected 14 cases of severe poisoning from nitrobenzole used as al)ortitacient. The earliest, which occurred in 1866, was in a girl of 18 who, when 5 months pregnant, took 10 grains of the drug. Preg- nancy was not interrupted but the girl was severely poisoned with cya- nosis as a prominent symptom. The cases showed that nitrobenzole is without any abortifacient properties and can destroy fetal life only when the mother is fatally poisoned. Spin- ner (Corresp. Blatt. f. schweizer Aerzte, Oct. 27, 1917). Infectious diseases provoke abor- tion in a large proportion of cases when the febrile period is reached. It occurs in about two-thirds of preg- nant women attacked by typhoid fever, especially during the earlier months. Uterine hemorrhage is usu- ally the first symptom observed. Thus Sacquin collected 310 cases, and found abortion in 199; while Alartinet found 66 abortions in 109 cases. Small-pox causes abortion in about 40 per cent, of the pregnant women it attacks and the mortality is about 50 per cent., but is nearly 100 per cent, in the confluent type. In varioloid the child sometimes remains unaf- fected. The disease may also develop during convalescence. Abortion dur- ABORTION (WRIGHT). 163 ing variola is apt to be attended with more than the ordinary hemorrhage. Arnaud has reported several serious cases occurring during convalescence after small-pox. The grave symp- toms are attributed to the retention of the fetus, which died during the acute stage of small-pox, and was fre- quently only expelled during or after convalescence. Measles is an infrequent complica- tion of pregnancy, but, as observed by Klotz, it causes abortion in the majority of such instances. Pneu- monia frequently appears as an addi- tional complication. Scarlatina is also infrequently observ^ed in preg- nant women, though it occurs com- monly as a complication of the par- turient state. Pneumonia causes abortion in about one-third of the pregnant women it attacks e^rly and in two-thirds of those which contract the disease late. In the latter cases the fetus, though viable when born, may soon die of the infection after birth. The sta- tistics of 213 cases of pneumonia during pregnancy published by Flatte showed that the pregnancy w^as inter- rupted in 118 cases, there being 42 abortions and 76 premature deliveries. Death of the mother occurred in 7? cases among the 213: a mortality of 35 per cent. The mortality of the mother w^as greater in premature de- liveries than in abortion. Pulmonary tuberculosis, owing to its exhausting influence upon the nu- tritional resources of the body, renders it unfit to carry the fetus to term when the morbid process is far advanced. Abortion is relatively frequent in such cases, its occurrence and the viability of the child depending upon the stage of the disease. In 385 cases in which others ad- vised interruption of pregnancy the writer was able to escape it in 278 instances. Onlj' when cough, nightsweats, evening fever, and loss of weight continue in spite of sanatorium treat- ment is abortion indicated. After the first 3 months, he inter- venes only if the lung process is mild or only recently flaring up; otherwise one cannot hope, to influence the disease. If patient has several living chil- dren, or if there is laryngeal tubercu- losis, or this is the first pregnancy in far advanced tuberculosis, he in- terrupts pregnancy and sterilizes the woman. With acute heart disease during a pregnancy he advises that the uterus be emptied by anterior colpohysterotcmy under lumbar an- esthesia after the acute manifestations have subsided. Von Jaschke (Monats. f. Geb. u. Gynak., Apr., 1920). Chorea, though a rare complication of pregnancy, causes abortion in one- half of the cases, and is especially observed in primiparae. If the de- livery occurs sufficiently late, the child may live, but is frequently afifected with chorea. The chorea sometimes ceases after delivery. Cardiac diseases influence preg- nancy when it is sufficiently marked to impair the general circulation. Acute pericarditis practically has no morbid influence on gestation, but chronic pericarditis is deemed per- nicious. Acute endocarditis assumes increased virulence during pregnancy, its tendency being to become ulcera- tive, and to entail a fatal ending. Icterus, in its various forms, some- times complicates pregnancy. Even simple catarrhal icterus may cause abortion, but in icterus gravis it occurs always and usually proves fatal. In the epidemic icterus of preg- nancy, the probability that abortion 164 ABORTION (WRIGHT). will occur is somewhat smaller, while the mortality is not as great. Preg- nancy not only aggravates even sim- ple icterus, but it increases the tend- ency to yellow atrophy of the liver. Paternal and Fetal Causes. — The influence of syphilis on abortion has been reviewed ; in most instances it is acquired from the male directly, either before or after conception, the disease being communicated to the fetus, in the latter case, through the placenta. In accord with Colles's law, the fetus may, as is well known, inherit the paternal syphilis, while the mother re- mains immune. Abortion may thus be caused through maternal or fetal syphilis acquired from the father. Any condition such as senility, al- coholism, overwork, etc., which tends to lower the vitality of the father tends also to weaken the offspring and pro- mote the tendency to miscarriage in the mother. Certain occupations which expose the patient to the action of certain poisons, mercury, phos- phorus, or lead, for instance, tend in the same direction. Besides the features which tend to compromise the development of the fetus that have been referred to, it is itself subject to injuries communi- cated from the exterior, blows, siiocks, penetrating wounds (knife, bullets, etc.), etc. The application of X-rays has recently been added to the list of known causes. Low or vicious attachment of the placenta, degeneration of the chronic villosities, hydramnios are the remain- ing main abnormalities which affect directly the fetus and cause its pre- mature elimination by the uterus. PROGNOSIS.— Considerable loss of blood may occur in a case of threatened abortion, and yet the pa- tient, when properly treated, proceeds to full term. Cases of spontaneous abortion unattended by complications practically always recover. The de- gree of antisepsis has much to do with the result however; while, for example, in Pinard's service where rigorous asepsis was observed the mortality was only 0.81 per cent. ; cor- responding cases (which included fa- vorable and unfavorable) outside his services reached 27.5 per cent. Out of 610 cases treated at the Boston City Hospital in 10 years ; 29 deaths, or 4.75 per cent. They included a large proportion of induced and neglected cases. The deaths include cases with pre-existing typhoid and pneumonia. With two exceptions those of the 29 deaths obviously due to the miscar- riage were caused by septic pneu- monia following a miscarriage be- tween 4 and 6 months. TREATMENT.— Treatment of Threatened Abortion. — W lien the symptoms of threatened abortion ap- pear we should endeavor to stop the morbid process, especially when the hemorrhage is not copious, the pains are not severe, -and there is no evi- dence of the escape of liquor amnii. Our chief aim should be to keep the patient absolutely quiet, by ordering her to bed, and relieve the pains due to uterine contractions by means of opiates in suitable doses. Opium seems to be better than morphine, even when the latter is given hypoder- mically. The tincture of opium, 30 minims (2 Gm.) should be given by the mouth, followed by 15 minims (1 Gm.) every hour, repeated three or four times if required. Or, better still. 2 grs. (0.13 Gm.) of the aqueous extract of opium can be given as a rectal suppositon,', and 1 gr. (0.065 ABORTION (WRIGHT). 165 Gm.) every hour afterward, three or four times if needed. If morphine be preferred, Yz gr. (0.032 Gm.) may be given hypodermically, and ^ gr. (0.016 Gm.) every hour, therefore, for three or four doses if required. An excellent plan when one wishes speedy effect from the opiate is to give at once ^ gr. (0.032 Gm.) mor- phine hypodermically, and 15 minims (0.92 Gm.) of tincture of opium by the mouth every hour afterward, or 1 gr. (0.065 Gm.) of extract of opium in a suppository every hour afterward for three or four doses if required. [Some physicians will consider that such dosage is large. Many physicians and ob- stetricians grew timid about the use of opium because of the violent antiopium riots that broke out in many surgical camps about twenty years ago, after Law- son Tait told the abdominal surgeons of the world that opium was an abomination which must be discarded in their work forevermore. The pendulum, has turned, however, and is going the other way. A. H. Wright.] We ought, of course, to consider that opium should be given with great care. At the same time, the writer thinks it absurd to give, for instance, 10 minims (0.61 Gm.) of tincture of opium by the mouth, three times a day, for the pains of threatened abortion. As a rule such doses will have no good effect, because they will not relieve the pains, and they may have a bad effect by causing constipa- tion. Opium does cause constipation, and thus interferes with elimination, but the writer does not admit that it causes complete -paresis of the intes- tines. Sepsis alone causes that kind of paresis. The constipation caused by opium can be easily overcome by the admin- istration of ordinary laxatives. If, however, the physician who has given opium in the case of threatened abor- tion is afraid to use mild cathartics for constipation, he might order an ordinary enema. Some years ago the administration of viburnum prunifolium was sup- posed to have a good effect in cases of threatened abortion. The result of recent experience does not indicate that such supposition is correct. The writer considers it practically worth- less. The fluidextract, Yz to 1 dram every three hours, or 10 drops every hour, with chloral hydrate 8 grains, have, however, been found effective in arresting uterine contractions when opium could not be used or when its constipating effects might prove detriinental. Or, chloral hydrate, 10 grains, and potassium bromide, 20 grains every two or three hours, may be preferable, since the hypnotic tends to insure the absolute rest and quiet that should be observed to obtain a sat- isfactory result. Codeine is preferred to other opiates by some obstetricians. Treatment of Inevitable Abortion. — There never has been, and probably never will be, a consensus of opinion among obstetricians as to the treat- ment of abortion. It seems conven- ient to consider that there are three general plans : expectant treatment, treatment by tamponade, forced dila- tation of the cervix and curettement. Expectant Plan. — The term expect- ant is not a good one as a rule, and it becomes most unsuitable if it is mis- understood. Lusk was perhaps the most prom- inent advocate of the expectant plan of treatment. He urged that, when in the third month the ovum is thrown off without the rupture of the mem- branes, the hemorrhage rarely as- 166 ABORTION (WRIGHT). sumes dangerous proportions, and explained hoAv llie uterine contrac- tions sometimes pressed the ovum into the cervix. During these uterine contractions the ovum descends and the upper portion of the body of the uterus retracts. Some coagulation of the blood takes place between the ovum and the retracted uterine walls, while the ovum forms a tampon which fills the cervix like a ball valve, and thus restrains the hemorrhage. When there is no interference, the OvT-im, five weeks. ovum, after being retained for a time as described, is frequently expelled entire, leaving the uterus in the best possible condition for satisfactory in- volution. In such cases, and they are by no means uncommon, nature has done well. AVhy should we try to improve or interfere with such mag- nificent Avork? Opinions still differ greatly as to whether active or conservative meas- ures are preferable, l)ut at the Strass- burg clinic, in charge of Fehling, active treatment is the usual course. A very important guide for the man- agement of the case is what she calls "latent complications," namely, that while nothing pathologic can be pal- pated, yet the patients complain of pains during internal examination. Tenderness of the vaginal portion of the uterus or tissues around indicates incipient inflammation, showing that the morbid process is not restricted to the endometrium but is extending beyond it. This calls for strict con- servative treatment, just as much as exudation in the pouch of Douglas or disease of tube or ovary. B. Engler (Corresp. Blatt f. schweizer Aerzte, July 21, 1917). Removal of the Uterine Contents. — It should be (lelinitely understood that, while nature is doing good work, we should watch carefully, and be ready to assist when her efforts have ceased to be efficacious. When the os and cervical canal are sufficiently dilated to allow the introduction of the finger into the uterine cavity, and the uterine contents are not extruded, we should interfere, and endeavor to empty the uterus. \Xc should presume, unless there is positive proof to the contrarv', that the ovum is intact, and should not be broken. The following course is recom- mended : Place the jiaticnt across the bed. in the lithotomy position, and with the external hand endeavor to depress the uterus through the ab- dominal wall until the index finger of the other hand (carefully asepticized) can be passed through the os and up to the fundus. An anesthetic is only occasionally required. Pass the fin- ger up on the lateral wall of the uterus imtil it is above the ovum, at or near the opening of one of the F'allopian tubes ; then pass it across the fundus to the neighborhood of the other Fallopian tube, and sweep down this wall, driving the contents of the uterus before it. In these manipu- lations try to avoid rupturing the ABORTIOX (WRIGHT). 167 ovum. If unable to remove the ute- rine contents in the way described, one should try the following Rotunda procedure : Take the finger out of the uterus and place it under the fundus, that is to say, in the anterior fornix if the uterus is normal in position, and in the posterior fornix if the uterus is retroverted. Sink the other hand into the abdomen and compress the body between the two hands. The ovum is then driven out of the uterus into the vagina and removed (Jellett). It is well to remember that there is a period between early and late abor- tion— say, in the latter part of the third month — when it is difficult, with the finger-tip, to make out the placenta, because it feels exactly like the endometrium. It is possible under such circumstances to make the mistake of imagining that the uterus is empty while the thin, broad placenta is completely ad- herent. In such a case it is better to try to remove this placenta by scraping with the finger-tip, as the use of the metallic curette under such circumstances is dangerous. Analysis of 750 cases of abortion of the out-patient department of the Chicago Lying-in Hospital, and treated at their homes. The routine treatment adopted in the 276 cases of threatened hemorrhage was absolute rest in bed, with morphine and codeine every four hours, with saline purgatives where needed. When malposition of the uterus was pres- ent, this defect was corrected. The pregnancy was saved in 72.8 per cent, of the cases. The inevitable abortions were treated bj- packing and curetting with the finger when possible, using the curette only when absolutely necessary, excepting in chronic cases. All the mothers re- covered. Summary of conclusions: Absolute rest was imperative; blood loss should always be prevented: cotton pledgets are preferable for tampons to gauze, being firmer; whenever possible emp- tying of the uterus should be done with the finger; laminaria tents are difficult to sterilize. Stowe (Surg., Gynec. and Obstet., Jan., 1910). Divergent views continue to exist regarding the relative advantages ot active and conservative treatment in non-septic abortion. According to the writer, curettage is necessary in 40 per cent, of non-septic cases treated expectantly. The curettage insures an empty uterus, prevents subsequent bleeding, shortens the patient's stay in the hos- pital, and is relatively harmless. D. S. Hillis (Surg., Gynec. and Obstet., xxxi, 605. 1920). The Tampon. — The vaginal tampon (or plug, as it is still termed by many in Great Britain) has been used for various obstetrical purposes for cen- turies. We believe that treatment by tamponade is the safest and best kind in all varieties of inevitable abortion, whether complete or incomplete. There are two kinds of tamponade: the vaginal and uterovaginal. raginal Tamponade. — In order to be efficient the vaginal tamponade should be properly done. Although it is one of the simplest of obstetrical opera- tions it appears that in the majority of cases it is imperfectly carried out. In the first place the vagina cannot be properly plugged w^hile the patient is lying on her back, or on her side. The patient must be put in the Sims (semiprone) position. The perineum and pelvic floor must be thoroughly retracted by a Sims speculum, and the vagina properly ballooned, so that its vault, thus distended, may be com- pletely filled by the material used for the packing. It is only necessary to pack tightly the upper two-thirds or 168 ABORTION (WRIGHT). three-fourths of the vagina. The mistake commonly made of packing tightly the entrance of the vagina generally causes great pain, and fre- quently retention of urine, by pres- sure on the urethra. The tampon checks the hemorrhage, dilates the cervix, assists further sep- aration of the ovum by damming back the l^lood, and induces uterine con- tractions. The writer, like Smellie, prefers an antiseptic plug, and uses Vagina ballema (gauze packing). material impregnated with 5 per cent, iodoform. A simple sterile plug is introduced by some, but an antiseptic phig is better. The former becomes foul ill about twelve hours, while the latter (when iodoform is used) re- mains sweet for two or three days. The ordinary iodoform gauze is not suitable however, because it is too coarse in texture, that is. too much like a sieve. The blood easily runs through it. Therefore, the writer prefers to use a rather fine cheesecloth impreg- nated with the iodoform. [It is prepared for me by Miss Margaret Lash, as follows : Take A yards of cheese- cloth (good quality) 27 inches wide; tear (not cut) into strips 4^ inches wide and full length ; sterilize these strips, and then boil in sterile water; wring them as dry as possible (having hands covered by sterile gloves) and thoroughly saturate them in the following preparation : 8 ounces of a 1 per cent, solution of carbolic acid in sterilized water, and enough Castile soap to make suds; 3 drams and 1 scruple of iodoform powder; mix thoroughly in sterile basin with sterilized pestle or glass rod. After thoroughly saturating the strips, wring as dry as possible, and pack the gauze strips one after another into sterilized glass jars, and seal down while moist. One strip 4j/2 inches wide by 4 yards long is ample for most vaginal tampons. This happens to be one-half of a square yard, that is, 3 feet by one foot and a half. A. H. Wright.] The method of procedure for early abortion is as follows: Place the pa- tient in the Sims position, introduce a Sims speculum, and let the assistant retract the perineum and pelvic floor (or use two fingers of one hand for such retraction, as recommended by Schauta) ; introduce the continuous strip of iodoformed cheesecloth, and firmly pack the vault of the vagina. In doing this one should use not the point of a sound or forceps with fine points, but something with a fairly large surface. My custom is to use the handle of a uterine sound when packing tightly. Continue the pack- ing until the upper three-quarters of the vagina is filled, and then allow the end of the strip to hang out at the vulva. If in a few hours strong pains occur, indicating that regular uterine contractions are taking place, take hold of the end of the strip and pull out the material forming the plug. It may be that by this time the ovum has been separated and expelled from the uterus. If such pains do not occur remove the tampon in twenty- four hours. There will then probably be some slight dilatation of the os, ABORTION (WRIGHT). 169 but not enough perhaps to allow the dinary iodoform gauze one-half to introduction of the finger. Introduce one inch wide is now pushed as far a second tampon as before. The tam- up as possible into the uterine cavity, ponade may be kept up with safety employing- a fine curved pair of uter- for many days (a week or more) if the ine forceps, a uterine gauze packer, plug is renewed every twenty-four or a uterine sound to do so. hours. It is unnecessary for the first In order to carry out the second two or three days to introduce any of stage of the operation the patient is the iodoformed strip inside the uterus, placed in the Sims position, and the because the aim is to cause uterine end of the narrow strip, the greater contractions that will expel the entire portion of which has been passed ovum. into the uterus, is tied to the wider If it is found, after the removal of strip used for the vaginal tamponade, the second or third tampon, that the After retracting the perineum and OS and cervical canal are sufficiently pelvic floor, the upper three-fourths dilated to allow the introduction of of the vagina is packed tightly in the the finger, we may explore the interior manner previously described, of the uterus, as recommended in con- If strong uterine contractions occur nection with the expectant plan, and the double plug and ovum may be endeavor to remove the complete expelled together. If no strong ute- ovum. If, however, a portion of the rine contractions commence withdraw ovum has come away, the uterovagi- tampon in twenty-four hours, and in- nal tamponade becomes the proper troduce a n^w one. This procedure procedure. means, of course, that the membranes It may be well now to repeat that w'ill be punctured, if they were not the object of the vaginal tamponade previously ruptured. This is suitable is to cause the expulsion of the en- for all cases of abortion between the tire ovum during early abortion, that end of the third and the end of the is, before the complete placenta is seventh month. In the seventh month formed. The object of the utero- we must consider the possibility of vaginal tamponade is to empty the the expulsion of a living child. In uterus in case of incomplete abortion helping deliver}- during this month, (whether early or late), and also in and sometimes in the fifth or sixth case of late abortion, that is, after the month, one may introduce a gum elas- complete placenta has been formed. tic bougie (English No. 12) within Uterovaginal Tamponade. — This pro- the uterus or a medium-sized rectal cedure is divided into two stages: 1, tube (H. U. Little), as recommended the packing of the uterus ; 2, the pack- by Krause, and follow with the ing of the vagina. In packing the vaginal tamponade. However, the in- uterus it is generally more convenient troduction of the gauze through the to place the patient on her back in the cervical canal and into the lower lithotomy position, on a couch, on a uterine segment, with the vaginal tam- table, or across the bed. Introduce a ponade, is generallv quite sufficient to weight speculum, seize the anterior produce efficient uterine contractions, lip of the uterus wuth a volsellum -phe treatment of abortion is consid- forceps, and use slight traction. Or- ered by the writer under three heads: 170 ABORTION (WRIGHT). (1) imminent abortion may be pre- vented by absolute rest in bed and the use of drugs like codeine and vibur- num prunifolium; (2) progressing abortion, and (3) incomplete abortion may be assisted to a spontaneous ter- mination by a hot vaginal antiseptic douche and vaginal gauze packing. An oxytocic should be administered in- ternally. If the result is not satisfactory after twenty-four hours, the partially dilated cervical canal should be packed with gauze and the vagina below tightly controls the bleeding, but aids in the expulsion of the placenta. He believes that the method is safe and efficacious, and prompt in its influence. Two to three drops of adrenalin solution mixed with 1 c.c. of physiological salt solu- tion is injected. Of course, careful asepsis must be maintained. In giving the injection it is best to use a Sims speculum. If results are not prompt, the injection may be repeated in a few minutes. Grasscr (Centralbl. f. Gynak., Nu. 25, 1909). Outline of Treatment in Abortion and Miscarriage. Ovum re- tained. Ovisac or placenta retained. FiBST Six Weeks of Preg- NANCy. Cervix closed. Cervical and vaginal tam- ponade. Uterine tam- ponade. Placental pieces or deeidua retained. Dull curette. Cervi.x open. Removal with one finger. Removal with ovum for- ceps under guidance of finger. I>ull curette. Seventh to the Thirteenth Week. Cervix closed. Cervix open. Cervical and vaginal tam- ponade. I Removal with one finger. Uterine tarn- Removal with ponade. one finger. Dull curette. Dull curette under guid- ance of finger. Fourth to the Sixth Month. Cervix closed. Cervix open. I Tamponade or Removal with dilate with two fingers, small Voor- hees bag. Tamponade or Removal with dilate with ^ one or two finger. fingers. Curette care- Removal with fully or dl- one finger, late to admit finger. I F. J. Taussig (Surg., Gynec, and Obstet.. May. 190J). filled with the same material. Uterine contraction will thus be usually incited and everything expelled. If too much bleeding is going on, the uterus may be emptied with the finger or placenta forceps, and ergot administered, two or three doses usually sufficing. H. J. Boldt (Jour. Amer. Med. Assoc, Mar. 17. 1906). Table containing the kernel of the operative indications. If conscien- tiously followed, it vyill. the writer believes, lead to considerable improve- ment in the practitioner's treatment of abortion and miscarriage. For several years the writer has been in the habit of injecting adrenalin into the uterine cervix in cases in which there was bleeding after abortion with retention of the placenta. It not only Conclusions based on the results in 2000 cases of miscarriage: 1. Spontane- ous emptying of the uterus takes place in but about 13.2 per cent, of all miscar- riages. 2. The likelihood of a miscar- riage to complete itself increases with the duration of pregnancy. 3. When it becomes necessary to use artificial means to complete the miscarriage, the finger followed by the curette in later miscarriages, and the curette alone in the earlier months of pregnancy, has given uniformly satisfactory results. 4. Experience has shown that where the cervix is extremely rigid it is better to introduce the curette and break up the fetus and placenta and remove them piecemeal than to attempt to dilate the cervix sufficiently to introduce the fin- ger. 5. Packing the vagina and lower ABORTION (WRIGHT). 171 segment of the uterus is an unsatisfac- tory and often unsuccessful method of emptying the uterus. No success what- ever was obtained in treating incom- plete miscarriages in this waj-. 6. Pack- ing is, however, of great value in two classes of cases: First, in exsanguin- ated patients to stop the hemorrhage and give the woman a chance to re- cover somewhat from the loss of blood before emptying the uterus. Second, when the cervix is very rigid, a tight cervical pack for twenty-four hours will soften it so that dilatation may be attempted with safety. 7. The results of artificial methods are as good as, but not better than, where nature has suc- ceeded in emptying the uterus. 8. Artificial methods are necessary in a majority of cases, however, simply because nature has failed. 9. In in- fected cases the essential thing is to empty the uterus. 10. The later in pregnancy miscarriage occurs, the smaller the liability to become in- fected, but the greater the likelihood of developing grave septic complica- tions if infection occurs. E. B. Young and J. T. Williams (Boston ^led. and Surg. Jour., June 22, 1911). In cases of hemorrhagic abortion the author has the uterine secretion examined at once, and if streptococci are found, the uterus is not evacu- ated but conservative treatment pur- sued. He does not believe the danger of fatal hemorrhage at an abortion sufficiently great to consti- tute a contraindication in the presence of a streptococcus infection. Neu (Munch, med. Woch., Nov. 19, 1920). Treatment of Incomplete Abortion. — Some authors state that the uterus may be emptied at once, the cervical canal bein,L^ dilated and the finger or curette or both being" used. Occasion- ally the finger may be used with ad- vantage when the cervical canal is well dilated, but we do not advise the use of the curette. Others hold that we should not interfere until there is decomposition of the ovum or danger- ous hemorrhage. We do not approve of this kind of expectant treatment. \\'ithout discussing these or other methods of treatment we recommend the uterovaginal iodoform tamponade for all kinds of incomplete abortion, wdiether occurring before or after the formation of the placenta. In these cases there is nearly always some dilatation of the cervical canal, gen- erally enough to allow the introduc- tion within the uterus of a narrow strip of iodoform gauze. If the canal which was once slightly dilated has again become so contracted that no gauze can be passed through it we may do the vaginal tamponade as be- fore directed, and thereby cause suffi- cient dilatation for our purposes. If we use the iodoform gauze or cheese- cloth instead of ordinary sterile gauze, we do not fear the danger of decom- position which 'is said by some to occur in the uterine cavity about the vaginal plug. If, however, one fears such an occurrence he should remove the vaginal plug in ten or twelve hours, instead of waiting twent\'-four hours, as we have generally recom- mended. The uterovaginal tampon- ade may be repeated several days if considered necessary. If after waiting one or two weeks the accoucheur has reason to fear that some portions of the egg have been retained, and there are no signs of sepsis, he may use a dull curette with great care. In the Michael Reese Hospital from 1912 to 1914, the treatment of incom- plete abortions consisted in tent dila- tion from 8 to 24 hours, digital empty- ing of the uterus when possible, otherwise curettage, followed by in- tra-uterine irrigation of 14 per cent. iodine. When the history and physi- cal findings were those of an incom- plete abortion, the uterus was emptied 172 ABORTION (WRIGHT). within 24 to 36 hours after the patient entered the hospital. This was done whether or not there was any tem- perature. Despite the cultural find- ings, which in 50 cases showed the usual number of anaerobic and aero- bic bacteria, the uterus was emptied in 24 to 36 hours. The value of this advice is indicated bj- the low mor- tality: .06 per cent, in 579 cases. J. E. Lackner (Surg., Gynec. and Obstet., XX, 537, 1915). The writer gives 1 c.c. (16 minims) of pituitary extract hypodermically before curetting for incomplete abor- tion and finds that it produces firm uterine contraction, which makes the curettement easier and almost blood- less. H. D. Furniss (Surg., Gynec. and Obstet., Sept., 1916). The seriousness of the retention of the ovular envelope or of placental structure has been considerably over- estimated in incomplete abortion. In- terference offers more risk of infec- tion than waiting. The average physician should content himself with vaginal tamponade for hemorrhage without any intra-uterine manipula- tion whatever. Removal of the tam- pon after 12 to 24 hours is usually followed by expulsion of the retained material, though exceptionally it may be necessary to repack the vagina. If the cervix is well dilated and the ovular mass is presenting at the cer- vix, the latter may be expressed by external compression of the uterine fundus or witlulrawn by means of a wide-blade placental forceps. Intra- uterine irrigation is condemned, and the advisability of vaginal douching is questionable. It may be necessary later, however, to dilate, curette, and pack the uterus to remove a so-called placental polyp. J. M. Fisher (Therap. Gaz., xliii, 233, 1919). Sepsis with incomplete abortion is a very serious complication. The curette, whether dull or sharp, should never be used when there is septic endometritis or even saprophytic in- fection. The finger may be used verv^ gently to remove debris when the cervical canal is sufficiently dilated. Then use an intrauterine douche of warm salt solution. After the douche is used introduce iodoform gauze (the coarser, the better) into the uterus, and place a certain amount in the vagina without packing tightly. Leave this in six hours, and then remove. After this removal keep the patient as much as possible in I*"owler's position, that is, a half-sitting position, to facili- tate drainage. Apart from such local treatment carry out the usual line of treatment recommended for puerperal infection. There is marked tendency among leading authorities toward conserva- tive treatment and limiting the use of the curette. The writer found that during the 5 years, inclusive from 1910 to 1914, there were treated, in the gynecologic wards at Jeffer- son Hospital, 296 patients, the great majority' of whom suffered from in- fection, man}- being well advanced and practicallj' hopeless. Many of them had undergone curettement prior to entering the hospital; 127 or nearly 43 per cent., were subjected to some surgical procedure after ad- mission. Careful analj'sis of the cases convinced him tiiat a smaller mortality would have occurred had these patients been received before they had been subjected to any surg- ical interference and the treatment confined to non-surgical measures. It should be remembered that, even admitting the retention of embryonic products, the infective organisms do not limit themselves to the local area. If they have not already in- vaded the blood, the manipulation necessary to explore and remove the retained tissue breaks down the bar- riers nature has erected against fur- ther invasion. Montgomery (Jour. Amer. Med. Assoc, Oct. 9, 1915). Curettage and Emptying the Uterus at a Single Sitting. — This operation ABORTIOX (WRIGHT). 173 may be occasionally justifiable when there appears to be urgent need of rapid emptying of the uterus. Whether this be true or not it is recognized as a legitimate operation by some of the best obstetricians and gynecologists in the world. A brief description of the procedure is there- fore given. Anesthetize the patient, place her in the lithotomy position "across bed," preferably on a Kelly pad. Prepare external parts and vagina as for vaginal hysterectomy, using espe- cially green soap and hot water, and a hot solution of Ivsol or other germi- cide. Introduce a weight speculum, secure the anterior lip of the cervix with volsellum forceps, introduce a branched steel instrument into the cervical canal, and dilate ; then intro- duce a curette into the interior of the uterus and scrape out its contents. Some operators then wash out the interior of the uterus with an antisep- tic solution, while others use the uterine iodoform tamponade. The advocates of the active treat- ment have not had as good results as those who use the expectant plan. While the latter gave a morbidity of 9.8 per cent, and a mortahty of 0.8 per cent., the active treatment gave a morbidity of 29 per cent, and a mortality of 9.8 per cent. The mor- tality with hemolytic streptococci was 31.2 per cent, with active treat- ment and zero with conservative. The strictly conservative treatment is reserved for the cases showing hemolytic streptococci. W. Benthin (Monatsch. f. Geburtsh. u. Gynak., xlii, 162, 1915). The writer found that it was possible to empty the uterus in the early stages of pregnancy in a few minutes with the aid of pituitrin and a curette, with very little loss of blood and without shock or collapse even in the most severe cases. No hot irrigations were required to as- sist in the expulsion of the fetus or placenta, nor were any irrigations or packing employed after evacuation of the uterus. The injection of 1 c.c. (15 minims) of pituitrin was given after tlie cervix had been dilated, while the patient was under the an- esthetic. In some instances the curette was unnecessary, strong pains beginning within a few minutes and entirely ex- pelling the uterine contents. Where the uterus was unable to evacuate itself, the curette was used to sep- arate the adherent placenta from the uterine wall, a procedure which caused practically no bleeding, even if the placenta was removed piece- meal, owing to the firm, hard condi- tion of the uterine wall due to the drug. The uterine cavity was wiped dry with gauze and swabbed with 5 per cent, iodine solution. It de- creased in size rapidly. J. L. Bubis (Amer. Jour, of Obstet., April, 1916). The writer recommends the follov/- ing course in septic abortion: Ex- pectant treatment is followed until the abortion is completed spontane- ously. If severe or protracted slight hemorrhage makes interference un- avoidable, the uterus is packed. The packing is removed after 12 to 24 hours and frequently the whole rem- nants of the abortion come away. li not, the packing has usually dilated the cervix sufficiently so that the uterus can be emptied manually. Re- peated packing is not favored. If the uterus is not empty after the removal of the packing, it is emptied preferably by hand, if necessary after additional dilatation with Hegar's di- lators and if the hand is insufficient, with the sharp curette. The longer the interval between the last rise of temperature and the operation the better. Packing afterward is avoided, unless necessitated by severe hemor- rhage. The uterus is never irrigated. Ergot is given only when hemorrhage exists after complete evacuation of the uterus. Vaginal douches are never given until at least a week after the abortion and then only for subinvolu- 174 ABORTIOX (WRIGHT). tion, not for purulent discharges. The patient is usually discharged 3 days after the last rise of temperature. Ries (Surg., Gynec. and Obstet., Apr., 1918). In febrile abortion the writer pre- fers merely to aid the natural forces in emptying the uterus. An ice bag is kept constantly on the abdomen to favor uterine contractions and 0.2 Gm. (3 grains) of quinine given every 4 or 6 hours. In 40 to 50 per cent, of cases uterine contractions usually appear after the second dose of quinine and result in expulsion of the ovum and placenta. All lavage, irrigation, and douches are forbidden. The vulvar dressings are changed 3 or 4 times daily. Cases in which abortion cannot be effected by this method are generally left alone for 3 or 4 da^'S, during which time the temperature usually returns to nor- mal. Curettage is then performed and is easier and less dangerous, as the uterine cavity is almost empty, the uterus small, and the uterine walls firmly contracted. A. Villar (Rev. argent, de obst. y ginec, iv, 10, 1920). Treatment of Criminal Abortion. — In the majority of cases of criminal abortion we have incomplete abor- tion with sepsis. We have to con- sider at the same time that some injury may have been done by the operator in his manipulations. One of tlie most common of such injuries is puncture of the uterine wall. The possibility of such injury should make us doubly careful in our methods of treatment. Treatment of Patient with "Abort- ing Habit." — When we have treated a certain patient for two or three threatened abortions which have be- come inevitable, the presence of syph- ilis should be carefully inquired into. If there is a syphilitic taint, or even a suspicion of it, both patient and hus- band should be placed under constitu- tional treatment. Malformations, dis- placements and other abnormalities of the uterus, and other conditions which act as direct causes of abortion may, of course, prevail in these cases, and should be carefully sought after. Apart from such considerations, rest and quiet are the important ele- ments in the treatment of such cases. The patient should be kept in bed or on a lounge from two days before the time of menstruation until three days after it ceases. In addition, if the patient is restless or sleepless, she should receive enough opium or other h3'pnotic, such as veronal, to make her sleep at least fairly well every night. During intervals she should have a moderate amount of exercise in the open air, and suitable tonics. Strong purgatives, vaginal douching, sports, and all kinds of fatiguing work should be carefully avoided. In case of re- troversion or retroflexion, the dis- placement should be corrected, in- troducing, if necessary, a suitable pessary, and leaving it until about the end of the fourth month. The automobile, particularly when used over rough roads is not infrequently a cause of abortion, especially when the fetus is sufficiently large to contribute a mechanical factor and weight to the mor- bid process. HorsebacV: riding likewise increases the danger. Editors. ABERRANT FORMS.— The rec- ognition of such conditions obviously is of great diagnostic importance. Missed Abortion. — The retention of the ovum within the uterus after its death is thus termed. The death of the ovum may occur before or after the formation of the placenta, but it is most apt to happen in the third month. This is probably due to the fact that at that time the egg is to some extf^nt loosened on account of the atrophy of a large portion of the ABORTIOX (WRIGHT) 175 chorionic villi. The death of the fe- tus frequently occurs, however, in the fourth, fifth, sixth or seventh month, and in a certain proportion of these cases the abortions are "missed." It is a singular fact, in connection with a case of missed abortion, that the dead ovum frequently or g-enerally remains in the uterus quiescent until term. In some cases the dead ovum still remains quiescent for an indefi- nite time, even after term. Although we cannot speak very definitely, we know that the dead ovum may remain in the uterus without any change in structure for one, two or more years. At least such appears to be the opinion of the majority of obstetricians at the present time. [This fact is sometimes of great impor- tance from a medicolegal standpoint. The case of Kitson vs. Playfair, which was tried in England about fourteen years ago, created intense interest. Dr. Playfair, the distinguished teacher and writer on ob- stetrics and gynecology, while treating in an ordinary professional way Mrs Kitson, the wife of Mrs. Playfair's brother, emp- tied the uterus, and found something like fresh placenta. Examination under the microscope confirmed his suspicion, and he expressed the opinion that there had been a recent incomplete abortion. As Mrs. Kitson had not seen her husband for over a year (he being in India and she in Eng- land) this meant a charge of immorality. Dr. Plaj'fair informed his wife, and Mrs. Kitson was dismissed in disgrace from her ordinary circle of relatives and acquaint- ances. The husband in consequence en- tered action against Dr. Playfair. It cost the latter altogether over $50,000. Many thought also that he was not justified in revealing a professional secret. A. H. Wright.] Mole. — When the dead ovum or a portion of it is retained in the uterus it is called by many a mole. AVhen there has been extravasation of blood between the layers of the membranes or into the substance of the decidua, coagulation takes place and the mass with its clot or clots is called a "blood mole." When there has been repeated extravasation of blood within the ovum the blood-strata undergo partial organization and the mass is called a "flesh mole." This flesh mole retains to some extent its attachment to the uterine wall, and in some cases after partial detachment may form new at- tachments. Under such circumstances the detention of the mass within the uterus may be much prolonged, as before mentioned. Treatment of Uterine Flesh Mole. — There is far from a consensus of opinion as to the treatment of such a mole. Some say leave it alone if there are not disturbing symptoms ; others say empty the uterus at once when a diagnosis is made. It hap- pens that a diagnosis is frequently difficult or impossible, and it also hap- pens that in the majority of cases the mole is expelled from the uterus with- in a reasonable time. The general practitioner will be on the safe side not to interfere unless serious symp- toms arise. If very serious symptoms do appear he should at once do the uterovaginal tamponade as before recommended. Hydatiform Mole (syncytioma be- nignum, vesicular mole, myxoma chorii). — This is a vesicular tumor within the uterus formed by sim- ple hyperplasia or cystic degeneration of the villi of the chorion at any time during pregnancy, but most fre- quently in the early months, and often after abortion. The accoucheur, in considering the symptoms of a supposed abortion, 176 ABORTION (WRIGHT). should ever keep in view hydatiform mole and chorion epithelioma, because early diagnosis and prompt treatment of both neoplasms are so extremely im- portant. The first symptom of the former is a discharge of a bloody fluid which is sometimes said to resemble currant juice. Our first suspicion is generally threatened abortion. If the discharge becomes more watery in ap- pearance, if vesicles are expelled, or if the uterus increases abnormally in size, we should suspect a vesicular mole. Generally we have to be guided by two symptoms, hemorrhage, and ab- normal increase in the size of the uterus. Treatment of Hydatiform Mole. — I'he condition is serious and prompt treatment is required. The uterus should be emptied as soon as pos- sible. The following is recommended : Dilate the cervical canal with Hegar's dilators, then introduce a sea-tangled tent, then plug the vagina as before described. If strong uterine contrac- tions come on within a short time re- move the tampon and tent. If such contractions do not come on remove the tampon and tent in twenty-four hours, then do the uterovaginal tam- ponade as thoroughly as possible. This will, as a rule, be sufficient to cause efficient uterine contractions which will expel the mole. If there is any doubt as to such expulsion ex- plore with the finger gently, and scrape the uterine wall with its tip. The metallic curette is especially dan- gerous in this case because the uterine w^alls are more or less weakened by the invasion of the cystic villi. Occa- sionally it may be advisable to use a dull curette, but this should be con- sidered a misfortune, and great care should be exercised. Chorioepithelioma (chorion epithe- lioma, syncytioma malignum, de- ciduoma malignum, choriocarcinoma). — This is a very malignant form of epithelioma developed from the epithelial layers covering the villi of the chorion. It is usually associated with abortion, and in 50 per cent, of the cases is preceded by hydatiform mole. We are told that it may occur after labor following full term, but the writer has not met such a case. Obstetricians have for some time con- sidered that this form of epithelioma is always associated with pregnancy. Some surgeons have said recently that tumors simulating chorion epi- thelioma have been found not only in women in the absence of pregnancy, but also in men, and tliat all such have arisen in pre-existing teratomata. Obstetricians, however, do not believe that such tumors are really chorio- epitheliomata. ^Metastatic deposits, even more malignant than the original tumor, soon appear in various parts of the body, especially in the vagina and lungs. Hemorrhage is the earliest and most persistent symptom. The flow is at first red, but soon becomes dark and offensive. The uterus grows rapidly and is often perceptibly soft in one or more places. A hemorrhage is serious when it becomes in the slight- est degree offensive. Scrapings from the uterine wall may be examined microscopically. Treatment of Chorion Epithelioma. — A radical operation is immediately indicated. The uterus, appendages, and metastatic deposits, especially if any be found in the vagina and vulva, should be removed. INDUCED ABORTION.— Induc- tion of abortion is very grave in any ABORTION (WRIGHT). 177 case, and should never be decided on without a consultation. Indications. — It may be said in a general way that, in any case where the life of the patient is imperiled by the continuation of pregnancy, abor- tion should be induced. In nearly all cases, however, when serious disease is present it should receive prompt and careful treatment. That death of the embryo or fetus is a positive indication for the induction of abor- tion need scarcely be emphasized. Tuberculosis. — It was a few years ago (and is now we fear) the custom of some physicians to induce abortion in all pregnant women suffering from tuberculosis. We have to consider, however, that in the light of our present-day knowledge tuberculosis is a curable disease in the pregnant Woman as well as in the non-pregnant one. If, then, our patient has tuber- culosis during pregnancy it is our duty to treat the tuberculosis and not to murder the unborn child. This should be our general rule. In a few exceptional cases (and they are very few), especially w'hen the morbid process is far advanced, the uterus should be emptied. Cardiac Disease. — In a large majority of women who have heart disease, pregnancy does not produce eflfects sufificiently serious to justify the in- duction of abortion. If, however, as happens in a small proportion of cases, especially when there is mitral stenosis, such symptoms as hemop- tysis, precordial distress, palpitation, and great debility appear, and grow steadily worse, under appropriate treatment, the induction of abortion should be considered. Excessive Vomiting of Pregnancy. — We have recently learned that the pernicious vomiting of pregnancy is due, in some cases at least, to peculiar disturbances of metabolism which produce a toxemia. Chemical exam- ination of the urine shows a decrease of the amount of nitrogen excreted as urea, and an increase of the amount excreted as ammonia. In normal pregnancy, the quantity of ammonia excreted (the ammonia coefificient) is 4 to 5 per cent. In pregnancy with this form of toxemia, it may rise to 10, 20, or 40 per cent., or even higher. Williams thinks th.at when the am- monia coefficient exceeds 10 per cent, the pregnancy should be immediately terminated. We have found, how- ever, that in some cases the ammonia coefficient may considerably exceed 10 per cent., and the patient may re- cover without the termination of preg- nancy. It is hoped that further in- vestigation will lead to conclusions which we shall all accept. We agree with A\ illiams to some extent, how- ever, and believe that when the am- monia coefficient reaches 10 per cent, the patient is in a dangerous condi- tion, and needs prompt and suitable treatment. If in spite of such treat- ment carried out for one to tw^o weeks she grows steadily worse, pregnancy should be terminated. The practitioner wdio does not de- pend on this chemical test should be guided by the symptoms and condi- tion of the patient. Indeed no one should neglect a careful study of all symptoms. It is very important that we should not w^ait too long. We have certainly much to learn yet re- specting this very perplexing subject. We have occasionally found that the results of interference even in appar- ently favorable cases are sadly dis- appointing. 1—12 178 ABORTION (WRIGHT). The most frequent conditions de- manding induction of abortion are the toxemias of early pregnancy, per- nicious nausea and vomiting, and in- abiHty to maintain the metabolism of the body. Intensive observation of these patients is required for com- puting the total intake and output " and the total amount of nourishment retained for 24 hours. Accurate laboratory research is necessary. Heart lesions with evidence of de- compensation also furnish grounds for therapeutic abortion. E. P. Davis (Therap. Gaz., xliii, 389, 1919). General Toxemia of Pregnancy. — No definite statement can be made as to the exact time when interference is desirable in case of general toxemia of pregnancy. Apart from excessive vomiting in connection with toxemia we fear especially eclampsia. Before the onset of convulsions the induction of abortion is very rarely considered necessary. Convulsions, as a rule, do not occur in the early months of pregnancy ; when they occur in the later months an immediate dcHvery is considered necessary. A vaginal Caesarean section is probably safer than rapid dilatation of the cervix with quick extraction. Both opera- tions, however, are serious, and the careful, conservative physician will prefer to resort to safer procedures. The importance of great haste in emptying the uterus has been grossly cxasrererated in recent vears. We think this is especially true as to eclampsia. Chronic NepJiritis. — Induction of abortion is not, as a rule, indicated in cases of chronic nephritis. Occasion- ally the symptoms grow so serious, in spite of suitable treatment, that the patient's life is endangered. Under such circumstances the uterus should be emptied. Disorders of vision dur- ing pregnancy are very serious m pa- tients who have chronic interstitial ne- phritis. Partial or complete blindness in such cases generally indicates a fatal termination. On the other hand, one may have absolute blindness (hie en- tirely to a state of autointoxication. In such a case the ophthalmic changes are not marked as a rule, and the sight generally returns soon after the uterus is emptied. Herringham (Brit. Med. Jour., May 7, 1910) states that this transient form of blindness is never found in uremia or associated with chronic interstitial nephritis. Retinitis. — AfYections of the eyes should be carefully studied. Retinitis should receive prompt attention. If the symptoms grow worse instead of better after treatment for a few days, interference may become necessary. In cases of retinitis with white plaques, and dimness or loss of vision, asso- ciated with serious albuminuria, abor- tion should be induced at once. Colin Campbell (oculist) agrees with Her- ringham and various modern pathol- ogists as to the great difference be- tween a retinitis due to an old chronic nephritis and a retinitis caused by autointoxication of pregnancy. He says the retinitis of pregnancy has a bright outlook compared with that of nephritis. Examination of the tirine will materially aid a coming to an un- derstanding of the condition. "In pre- existing nephritis the quantity is usually greater, the urea and nitrogen more nearly full normal, and the albumin and casts more abundant. In pre-eclamptic cases the uric acid and the amidoacids are markedly increased" (Can. Jour, of Med. and Surg., Oct., 1910). It may be stated in a general way that such untow^ard symptoms occurring early are much more serious than similar ABORTION (WRIGHT). 179 symptoms which may appear late in pregnancy. Pyelitis. — PyeHtis due to toxemia of pregnancy is not very uncommon, although, until recently, it was not recognized as a separate entity. In- terference with pregnancy is not gen- erally required. If, however, the tem- perature keeps above normal for four weeks; if there is much pus in the urine ; if the leucocyte count is high, abortion should be induced. It is better if possible, however, to defer interference until the child has be- come viable. Antc-partum Hemorrhages. — Hemor- rhage from placenta praevia is our chief concern in this connection. If inter- ference becomes necessary we should employ the vaginal tamponade, and should never dilate the cervix to the slightest degree. If the hemorrhage is increased by complete or partial sep- aration of a placenta normally situateil the same rule as to treatment applies. Such hemorrhages do not occur fre- quently before tl.e child is viable, and, consequently, need not be discussed in detail here. Retroflexion of the Uterus. — When serious symptoms appear because of retroflexion or retroversion of the uterus, and the misplacement cannot be corrected, it mav become necessarv to interfere. In the majority of such cases abortion takes place without any interference. Contracted Pelvis. — The induction of abortion in cases of contracted pelvis was for a long time considered indi- cated. We hope it is generally con- ceded now that such a procedure is both incorrect and sinful. We have learned in recent years that conservative Caesarean section, done at the proper time with reasonable care and skill, is one of the safest and best operations now known to surgery. Such having been demonstrated, we have done well in ceasing to destroy unborn children because of contracted pelvis. Hydramnios. — When the hydram- nios causes the distention which seri- ously afl:ects the mother's health we may have to consider the desirability of emptying the uterus. In such cases, however, we can generally wait until the child becomes viable. Appendicitis, Ovarian Tumor, and Other Abdominal Grozvths. — Abortion should not be induced for any of these conditions. The ordinary operation for the disease or new growth should be performed. Goiter. — As a rule there should be no interference, at least until the child is viable. Myoma Uteri. — No interference with pregnancy is indicated as a rule. In a limited proportion of cases one or more fibroids may be so situated that delivery in the ordinary way is a physical impos- sibility ; but. even under such circum- stances, the induction of abortion is very rarely indicated. We may, how- ever, meet a uterus in which the growth would interfere with normal delivery, but in this case the child might be delivered by Caesarean section if pregnancy went on to term. Women with very bad fibroids seldom conceive, and when they do early abortion is apt to occur. Chorea. — In a certain proportion of severe cases of chorea the patient goes from bad to worse, notwithstanding suitable treatment. In very serious cases the woman grows worse very rapidly and dies unless the uterus is emptied. In many cases this serious procedure, unfortunately, does not save the patient. 180 ABORTION (WRIGHT). In many cases pernicious anemia in pregnancy seems to be due en- tirely to the pregnancy. When un- treated, it usually results in pre- mature labor, fetal death, or death of the mother. In metaplastic anemia developing during the first 3 months, abortion should be induced at once. Later, especially when hypoplastic, the patient should be treated medi- cally at first, and pregnancy inter- rupted later. A. Frcrs (Rev. argent, de obst. y ginec, iii, 430, 1919). Method of Inducing Abortion. — For the inchiction of ahortion we employ the methods and procedures generally used Amnionic sac containing embryo and waters. The thick decidua retained in uterus. (Seven weeks.) in cases of inevitable abortion (which see). When speaking about the treat- ment of the latter we had in view the fact that nature, chiefly through uterine contractions, and hemorrhages, had done something, perhaps much, in the process of abortion. The ovum has been more or less loosened from its at- tachments, and the cervix has perhaps been more or less dilated. In consider- ing the induction of abortion, we as- sume, on the other hand, that the ovum is pretty firmly attached to its moorings, and that the cervical canal is not dilated. Under such circumstances it is more difficult to empty the uterus. The fol- lowing recommendations are made for the induction of abortion at different periods of pregnancy up to the seventh month. This course seems advisable, although it will mean a certain amount of repetition : — Tn any case prepare the patient as for vacrinal hvsterectomv, or as has been for curettage, previously described. Pregnancy, three months, showing fetus below. Placenta formed. First or Second Month. — Introduce a vaginal tampon of iodoform cheese- cloth as before described. This may be removed, and reintroduced, every twenty-four hours for five or six days. In many cases these vaginal tampons will not produce the desired result, even in five or six days. Under such cir- cimistances one may introduce a narrow strip of iodoform gauze within the uterus after the first or second day. If, in doing this, one punctures the mem- ABORTION (WRIGHT). 181 brane, no serious harm will be done. After such introduction, practise vagi- nal tamponade. It may be necessary to do more than the introduction of the gauze ; if so, adopt the old-fashioned method of introducing a uterine sound, and purposely puncture the membranes if possible. This is suitable, especially in cases of pernicious vomiting, because such puncture allows the escape of the liquor amnii, and such escape often causes the serious symptoms to subside immediately. It happens that in certain cases it is difficult to puncture the mem- branes because the deciduum is thick, tougli and elastic. Third Month. — Carry out the methods recommended for the first and second months. There is less chance of causing the expulsion of the entire ovum and on that account it is not well to wait long before invading the interior of the uterus. Fourth and Fifth Months. — Practise a uterovaginal tamponade as before described as rapidly and thoroughly as possible. Sixth and Seventh Months. — ^Intro- duce a vaginal tampon, remove in twenty-four hours, place patient in lithotomy "across bed" position : intro- duce a weight speculum, seize the anterior lip of the cervix, pass a gum- elastic or hard-rubber bougie, or a medium-sized rectal tube within the uterus, between the membranes and uterine wall to the fundus if possible. Then place woman in Sims's position, and plug vault of the vagina tightly. Labor will generally come on in a few hours, and the uterine contents will soon be expelled. It is sometimes ad- visable to introduce the bougie in the fifth month. We find that in some cases the tam- ponades are not efficient, and we are compelled to adopt more forceful pro- cedures. As before mentioned we think the use of the metallic dilator and sharp curette in the "single sitting" operation is always dangerous. If this statement is true, or even half-true, it is sad to notice that some of our ablest authors in recent textbooks say that "the in- duction of abortion is practically free from danger if perfect asepsis is observed." This operation is especially dangerous in the class of cases included in this chapter because the patient is generally in a bad physical condition from the complication which calls for the termination of pregnancy, as, for instance, pernicious vomiting. It is generally an easy matter, espe- cially after a vaginal tampon has been in place twenty-four hours, to dilate the cervix with the Hegar dilators suffi- ciently to allow the introduction of the gauze within the uterine cavity. We also recommended the use of the laminaria (sea-tangle) tent for dilata- tion. It is said, however, that there is great danger of infection from the use of any tent for such purpose. There was, of course, much reason for such fear many years ago when the sponge, tupelo and laminaria tents were not sterile, and, in addition, were not used in an aseptic way; but during recent years we have been able to get excellent sterile laminaria tents that are perfectly safe if used in a cleanly way. Similar objections have been raised against tampons because they also were unsafe as used many years ago, but the tampon medicated with iodoform or other suitable antiseptic is as safe as anything that can be introduced within the uterine cavity. It is thought by some that there is danger from the use of the bougie according to Krause's method, but, if the bougie is made per- 182 ABORTION, TUBAL (DEAVER). fectly sterile by boiling and is carefully used, the danger therefrom is very sliglit. It is well to remember, how- ever, that there is always some danger in connection with any obstetrical operation through want of care on our part. We should ever make a con- tinuous effort to guard against such danger. A. H. Wright, Toronto. ABORTION, TUBAL.— DEFINITION.— Early interruption, i.e., abortion, is the natural outcome of extra-uterine pregnancy, whether by reasons of insufficient blood- supply or unfavorable mechanical conditions for the continued develop- ment of the fetus. [A brief review of the history of this im- portant subject ought to possess for us more than ordinary interest because of the impor- tant role played in its development by one almost of our own number and generation in whom we may take a pardonable local pride. I refer to the illustrious and lamented John S. Parry. He was not the first to write upon the subject. Indeed, Albucasis, the Arabian, in the eleventh century recognized and described a case of extra-uterine preg- nancy. Nor was he the first to grasp the possibilities of operative treatment in the emergency of rupture. That was proposed by Harbert, of New York, in 1849. The merit of Parry consisted not only in grasping the significance of the catastrophe and the correct mode of meeting the emergency, but in applying his philosophical mind and schol- arly attainments to the production of a mono- graph which by its masterly marshaling of facts and lucidity of deduction should have quieted the doubts of Thomas. He was able to collect for his book, which was published in 1876, 500 cases reported in the literature. Of 499, in which the result was stated, 366 died and 163 recovered. Of the deaths, 174 had been from rupture. Of these deaths 81 had died within 24 hours. These figures were his text. He began his sermon with this sentence: "From the middle of the eleventh century, when Albucasis described the first known case of extra-uterine preg- nancy, men have doubtless watched the life ebb rapidly from the pale victim of this acci- dent, but have never raised a hand to help her." Then, though not himself a surgeon, he points out the plain surgical indications. In the same year as the publication of his monograph he died, doubtless depriving the world of one who was destined to become one of its greatest figures in the advance- ment of medicine. Parry was a pupil of my father, who often used to speak of his stu- dious habits and scholarly grasp. He was by nature fitted for mental leadership. The honor of performing the first opera- tion for this emergency went to Lawson Tait ill 1883. He had been earnestly solicited to operate for this condition ii> 1881 by a physi- cian who had correctly diagnosed a case of rupture with internal hemorrhage. He re- fused, and the patient died shortly after. Unfortunately the first patient operated on died also, but his change of heart was com- plete, and, correctly attributing his failure in the first case to faulty technique, he altered his method and continued to operate all such cases. Of the next 40 cases only 1 died. Truly a brilliant record which was not long ill converting the medical fraternity. The original microscopical preparations of Tait in which he demonstrated his ideas on extra-uterine pregnancy and pelvic hemato- cele which, before him, were in a very con- fused state are still to be seen in the mu- seum of the Royal College of Physicians in London. There are many other names of more or less importance in connection with the de- velopment of the subject, but these two are central and all we have space to consider. John B. Deaver.] SYMPTOMS.— The symptoms of extra-uterine pregnancy include those due solely to the condition of preg- nancy and those which arise only from its abnormal situation. Inas- much as the majority of cases termi- nate within three months, at which ordinary signs of pregnancy are not usually pronounced, we do not often get much help from the symptoms belonging to the first group. Yet ABORTION, TUBAL (DEAVER). 183 such symptoms and signs as enlarge- ment of the breasts, the presence of colostrum, cessation of menstruation, increased vascularity of the genitalia, softening of the cervix and body of the uterus with slight enlargement, disturbances of the bowels or bladder, morning nausea, and the abnormal appetite, cravings or sensations which the multipara sometimes recognizes, are occasionally of confirmatory value. It would be desirable to make the diagnosis before rupture were it pos- sible to do so. Unfortunatelv a large percentage of cases give such trifling evidence of the true condition, if indeed there be any prodromal symp- toms at all, that no suspicion is aroused. Still it is occasionally pos- sible to make the diagnosis and it should be our effort to do so. One operator, Baldwin, of Columbus, Ohio, has reported 11 such cases. Lejars holds that a prolonged continu- ous blood-stained uterine discharge is an important aid in dififerentiating tubal abor- tion; even if the proportion of blood is small its persistence for two up to five weeks is characteristic, and absence of blood in the vaginal discharge is strong evidence against a recent hematocele. The slight hemorrhage seems to persist longer after tubal abortion than after rupture. Incomplete expulsion of the ovum is also liable to keep up the hemorrhagic dis- charge, and the writer relates some in- stances of such retention of the placenta with the tube open and of total retention with the tube closed. The small encap- sulated collection of blood may be taken for a fibroma, and the resulting disturb- ances for inflammatory processes in the adn»xa or in the uterus. Certain cases of tubal abortion have been diagnosed as a hemorrhagic metritis, and the uterus was curetted when this organ was sound and the trouble was in the tube beyond the reach of the curette. According to Plolden a sign of tubal pregnancy is a more or less striking pale- ness of the cervix. The absence of this paleness does not, however, exclude this condition, but its presence, when not due to obvious other causes, is almost pathog- n&monic. It is only present, however, in those cases in which there is bleeding from the uterus. Editors. The diagnosis in these cases rests upon : first, a consideration of the his- tory. Important points for considera- tion are the age of the patient, exposure to pregnancy and the pre- sumptive signs and symptoms, a history indicative of an antecedent tubal inflatnmation, a previous period of sterility usually of some years. This last point has been observed by all students of the condition and Parry remarks on what he calls "the previous inaptitude for conception" of these patients. Amenorrhea of shorter or longer duration is a fairly constant feature and is followed in the majority of instances by irregular bleeding from the uterus, sometimes profuse, some- times a mere staining. The history of passing bits of tissue or the deinon- stration of decidua in the discharge is important. Pain if felt before rupture consists frequently in vague uneasy sensa- tions in the pelvis. Sometimes it is more severe, colicky in type and ac- companied by nausea. In cases which show any of these suspicious symptoms an internal ex- amination should not be neglected. The demonstration of a pelvic mass lying outside of the uterus, in the presence of a probable pregnancy, is a very suspicious circumstance. If this mass should correspond in size with the duration of pregnancy, if it should be located in the course of the tube, if it be movable, moderately soft and very tender, we may fairly 184 ABORTION, TUBAL (DEAVER). conclude we are dealing with a case of extra-uterine pregnancy. It must be remembered that it is sometimes easy to mistake a retroflexed preg- nant uterus for an extra-uterine preg- nancy. A study of 36 cases simulating tubal pregnancy by Crossen showed that the following conditions may be mistaken for it: 1, an acute exacerbation of a dormant gonorrheal pyosalpinx; 2, sudden exten- sion of a uterine gonorrhea to the tubes and peritoneum; 3, an early abortion if associated with salpingitis or a tumor; 4, an irregularly softened, misplaced, hyper- esthetic uterus associated with tubal en- largement; 5, an unsuspected tumor asso- ciated with symptoms of early pregnancy; 6, ovarian hemorrhage or tubal hemor- rhage from other conditions; 7, sudden and rapidly progressive salpingitis, appen- dicitis, and gastrointestinal perforations. A positive diagnosis of unruptured ectopic pregnancy or tubal abortion should be made in the vast majoritj' of cases. In his service at the Long Island College Hospital, and in over 250 personal cases, a positive diag- nosis was made in over 85 per cent, of the cases. This is due to the fact that a very careful history was taken and a thorough physical examination made in each instance. The condi- tions, pathological or mechanical, that may cause a delay in the prog- ress of the impregnated ovum are always indicated in the history if the attending physician or surgeon takes the trouble to correlate the facts as stated by the patient. The diagnosis of ruptured ectopic with the conse- quent hemorrhage and shock is ob- viously very much easier to diagnos- ticate. J. O. Polak (L. I. Med. Jour., xii, 121, 1918). Often before a diagnosis can be made, usually before the diagnosis is made rupture of the tube or extensive separation and hemorrhage from the placental site supervenes. It was formerly thought that rupture was the most common outcome of tubal pregnancy. More careful examina- tion of the specimens, however, has shown us that in many cases of sup- posed rupture we are dealing with a case of tubal abortion with hemor- rhage from the site of implantation. Moreover, hemorrhage from this source, while less violent as a rule than in rupture, may be very severe and even fatal. Frequently, however, it is comparatively slow and by slow leakage is responsible for the majority of hematoceles which we find. Recent statistics indicate that these tubal abortions occur more frequently than does rupture. The tragic stage, how- ever, may follow either process. [The idea that rupture is not so frequent as has been supposed and therefore an extra-uterine pregnancy is not so danger- ous a condition is fallacious. It is a mat- ter of common knowledge that tubal abor- tion may give rise to a condition as serious as any of the accidents of ectopic preg- nancy. I should not feel it necessary to insist on this fact were it not for an im- pression which is going abroad in regard to treatment, which I shall consider later. JoH.v B. Deaver.] There are instances in which a strong presumptive diagnosis can be made and for lack of which the pa- tient suffers. There is usually a ces- sation of menstruation for one or more periods, and in this case, with rupture threatening, it is usually re- established, irregular as to time, and of a tarry, sticky character which, ac- cording to some observers, is pathog- nomonic. The pain is usually cramp- like, occurring at intervals for sev- eral days, and following it there is a dark, sanguineous discharge, probably due to a partial rupture of the gesta- tion sac. Microscopic examination will reveal traces of decidua in most cases. A careful and thorough exam- ination is advisable and great care should be employed to avoid ruptur- ing the sac. L. G. Bowers (Jour. Amer. Med. Assoc, Feb. 12, 1910). ABORTION, TUBAL (DEAVER). 185 Pain is a very important symptom. It is sudden and acute in its onset; is located in the affected tube; is dis- tinct but rarely- ver\- severe prior to rupture (Zinke); and the attacks soon pass off. It is generally sickening in character, and it is usually the one symptom which induces the patient to visit her physician.' The tubal cramps result from an attempt on the part of the tube to expel the ovum or the blood which has exuded into its caliber. Considerable blood may escape through the fimbriated ex- tremity in this way, causing slight localized peritonitic attacks with re- sultant adhesions. The history of colicky attacks may cover several weeks before the final rupture of the sac. A vaginal exploration shows an exquisitely sensitive mass b'ing in close juxtaposition to the uterus, a strongly presumptive diagnosis of the condition may be made. The enlarged tube can readily be palpated bimanually in most cases, unless the abdominal wall is very rigid or un- duly thick. Such a tumor is uni- lateral, in distinction from inflamma- tory and purulent affections of the tubes, and while partially fixed it is not firmly adherent, presenting a board-like rigidity, as in the case of a pus-tube. It can be readily felt through the vaginal vault, and is commonly the seat of distinct arterial pulsation — another feature which is generally absent from inflammatory conditions of the tube. Dorland (Jour. Kans. Med. Soc, Nov., 1915). Of the 75 cases of bilateral tubal gestation reported in the literature, about 41 may be considered as sim- ultaneous gestations. But 8 of these cases are doubtful, reducing the fig- ure to 33 cases. Practically the diag- nosis of bilateral pregnancy is never made before intervention. On inter- vening for a tubal pregnancy, the annex on the opposite side should always be examined. If a hematosal- pinx is found it must always be re- moved. Proust and Buquet (Rev. de g\-nec. ct de chir. abd., xxiii, 353, 1916). Abdominal pain was present in all cases, varying from the classical crisis with the following shock from hemorrhage to the more or less con- tinued abdominal distress, which brought the 36 patients for examina- tion to the writer. The former con- dition with its clearcut evidence of intraperitoneal hemorrhage is not usually mistaken, but the slow process with its distress from tubal disten- tion or slight rupture is very confus- ing. In a case of irregular bleeding and abdominal pain, one must have constantly in mind 3 conditions, namely, intra-uterine pregnancy with threatened abortion; inflammatory tubal disease, especially hj-drosalpinx and pyosalpinx, and extra-uterine pregnancy. C. B. Lewis (Jour. Amer. Med. Assoc, Sept. 21, 1918). In 183 cases of ectopic pregnancy sudden onset of abdominal pain oc- curred in less than half of the cases, colicky pains in the lower abdomen in a little more than one-third, and abdominal tenderness in four-fifths. Vaginal examination showed the uterus enlarged in nearly one-third, and a palpable mass, which was usually tender, was found in one of the fornices or the cul-de-sac in over two-thirds. The temperature on ad- mission was above 99 degrees in nearly three-fifths of the cases. Fever was more frequent and rose higher in those in which the internal hemor- rhage was greatest. The most frequent error in diag- nosis was acute or chronic tubal in- fection, and the next, abortion and acute appendicitis. Usually a careful history and physical examination will lead to a correct diagnosis in un- ruptured cases. H. F. Lewis (Ills. Med. Jour., xxxvii, 301, 1920). Rupture is the most serious acci- dent of ectopic g'estation. It may take place very early and be the first symptom. Cases have been reported of rupture in the first or second weeks of pregnancy. Usually it occurs in the second of third months, but occa- 186 ABORTION, TUBAL (DEAVER). sionally may be delayed into the later months. Secondary rupture may oc- cur at any time after primary rupture up to term. Rupture is usually ushered in by severe lancinating^ pain in the hypo^s^astrium, accompanied by sliock, sometimes by syncope and frequently by nausea or vomiting. of the abdomen which is readily dis- tinguished from the usual rigidity of inflammation of the peritoneum. There are the symptoms of rupture and of hemorrhage per se. They are not always so frank and outspoken and in order to be sure of our ground it is frequently necessary to bring to Differential Diagnosis between Extra-uterine Pregnancy and Early Abortion Based on a Careful Study of 28 Cases. Extra UTERINE Pregnancy. 1. Advent is sudden. 2. Pain is severe very early. 3. Blanching of the face early. 4. Pulse very feeble and rapid early. 5. Hemorrhage usually not severe, but per- sists, even after the uterus has been thoroughly emptied. 6. At first there is no elevation of tem- perature, and later it is rarely above inr F. 7. At one side of the uterus there is usu- ally a very tender tumor, which is, as a rule, movable. 8. Boggy feeling behind the uterus. 9. Usually the cervix is very slightly open. 10. Shreds, decidual membrane and blood only escape. 11. Late there will be marked diminution of the hemoglobin (30 per cent, to 70 per cent.). 12. Rarely, if ever, polynuclear leucocytes. 13. If the cul-de-sac of Douglas is opened, blood will escape with possibly an embryo. Ralph Waldo (Archives of Diag., Oct., 1908) Early Abortion in Uterine Pregnancy. Rarely sudden. Not severe early. Blanching of the face late, if ever. Pulse strong and full until late. Hemorrhage usually severe early and mark- edly, diminishes after the uterus is emptied and ceases entirely in a few days. Frequently, especially if there is sepsis, the temperature is very much elevated. There is no tumor unless there is infection, and then it is rarely movable. Not present. It is open, especially if part of the products of conception are still in the uterus. An embryo may be found: if not, the mi- croscope will show chorionic villi. No marked diminution of hemoglobin. Frequently present, especially if there is in- fection. No blood will escape. Following this the symptoms of in- ternal hemorrhages make their ap- pearance. Increasing pallor, rapid and weak pulse, sighing and labored respiration and air hunger, dimming of vision, with increasing but slight distention of the abdomen, signs of fluid in the flanks, general abdominal tenderness most marked in the hypo- gastrium and a peculiar doughy feel our aid the history and the internal examination. In this condition as in so many others, the classical picture in toto is rarely seen and it has happened, parado.xically enough, as Douglas remarks, that many more diagnoses are made nowadays since the integrity of all the classical symp- toms have been repeatedly attacked than when a clear average picture had ABOPIIOX, TUBAL (DEAVER). 187 been drawn and accepted. It will do then to know that the three cardinal symptoms are pain, menstrual irregu- larities and tumor if w^e appreciate their variability. Conclusions based on a study of 214 cases : 1. Irregular flowing seems to play the important part given it in the books as a symptom of extra-uterine pregnancy. 2. The importance of a long period of sterility as a cause of extra-uterine pregnancy does not seem to be borne out by these statistics. 3. Conditions possibly leading to extra- uterine pregnancy: The fact that cystic ovaries, disease of the opposite tube, adhesions, or a previous miscarriage occurred in over 83 per cent, of 202 cases is suggestive, and is in agree- ment with authorities as to the possible relation of such conditions to extra- uterine pregnancy. 4. The fact that in only 26.5 per cent, of 207 cases the pain was sudden is of interest. In about three-fourths of the cases the sudden severe pain was preceded by pain of less severity, coming on gradually. 5. Of considerable interest is the leucocytosis observed in the cases in shock. This is apparently a perfect example of leu- cocjtosis after hemorrhage. The find- ing of a temperature of 100° or over in 43.4 per cent, of the cases, and of a temperature of 101° or over in 14.4 per cent, of cases, is also of interest. Ordi- narily it is supposed these cases rarely have any fever. Coues (Boston Med. and Surg. Jour., May 11, 1911). [The question of great and timely interest in connection with the treatment of extra- uterine pregnancy has to do with the man- agement of the case at the time of rup- ture, with associated hemorrhage and shock. Thanks to the early operation these com- plications are rare nowadays, but I fear, if the advocates of delayed treatment secure a following in the profession, that these cases may occur more frequently, and that cases which would be noted in the statistics of extreme conservatives as cures will later succumb to a condition which is the direct result of the Fabian policy. John B. Deaver.] COMPLICATIONS.— I have al- ready pointed out that spontaneous cures may occur without leaving a dangerous condition behind and have remarked on the rarity of such a favorable outcome. jMore usual is it for a collection of blood, often very large, to be left as a foreign body in the peritoneum. These collections or hematoceles excite a reactive peritonitis w^hich serves to glue together the intestines and encapsulate the mass of clots. Absorption and organization of such a clot may take place, but is usually very slow. In the mean time not in- frequently infection occurs. The danger of this is apparent when we realize that an hematocele is nothing but a most inviting medium for bac- terial growth, situated 'about the rectum or lower bowel, which harbors the most virulent bacteria. [An infected hematocele is a serious con- dition and demands prompt evacuation and drainage. This is best done by way of the vagina, if possible. At times it is necessary to attack it by the abdominal route, accept- ing the danger of a subsequent peritonitis. JoHX B. De.aver.] Obstruction of the bowel is men- tioned by Parry as the cause of death in a number of instances. The mechanism of this is by the peritoneal adhesions set up by the old extrava- sation of blood or a degenerated fetus in neglected cases. Case of extra-uterine gestation sac which ruptured into the large intestine. A five-months fetus with cord and placenta was passed from the rectum, and the patient recovered. Martin (Miinch. med. Woch., Aug. 21. 1906). A pregnancy which is allowed after rupture to develop free in the ab- domen or in the broad ligament later furnishes a very difficult problem to 188 ABORTION, TUBAL (DEAVER). the surgeon owing to the danger in dealing with the placental site, and the mortality in such cases is much higher than in tlie early cases. Left entirely to itself the fetus often be- comes infected, and the earliest records we have of extra-uterine preg- nancies are of cases in which this oc- curred, the resulting abscess later spontaneously discharging through the abdominal walls, when its nature was surmised by the appearance of degenerated fetal parts in the dis- charge. Sepsis, exhaustion and death were noted in 54 of Parry's cases. A new sign in ruptured extra-uter- ine pregnancy was identified by the writer. The patient, a woman of 38 years of age, suddenly developed ab- dominal pain and distention. Three weeks later, the Jiiiihilical region was bluish black, although she gave no history of injury. On opening the abdomen the writer found a right- sided extra-uterine pregnancy, and al)Out lYz quarts of free blood in the abdomen. A case is reported by Ransohoflf, where a man, 53 years of age, in whom at operation rupture of the common duct revealed much free bile in the abdomen. As he showed a similar discolored area the writer concluded that the l)luish black ap- pearance of the umbilicus in his own case was due to intra-abdominal hemorrhage, and the presence of the nodule to the side of the uterus es- tablished the diagnosis of extra- uterine pregnancy. T. S. Cullen (Trans. Amer. Gynec. Soc. ; N. Y. Med. Jour., Aug. 17. 191S). ETIOLOGY AND PATHOGEN- ESIS.— In attemjUing to get a clear idea concerning the causation of extra- uterine pregnancy, one is quite awed and overcome by the vast number of hypotheses which have been advanced to account for this curious anomaly. fit is not surprising that there is still much obscurity in the etiology. A correct understanding of the pathology of any condition presupposes a fairly exact knowledge of the normal physiology of the parts. There still exist many prob- lems connected with maturation, ovula- tion, impregnation, implantation and de- velopment. .Some of these problems carry us well back into the shadowy realms of the beginnings of life itself, that ultima Thule of the biologist. The incompleteness of our information concerning these abstruse secrets of nature forces us here, as in so many other medical problems, to resort to the meth- ods of induction and experience, and if we have not yet arrived at the point where we may safely take the inductive hazard it is because we may not yet have appreciated fully the saying of old Am- broise Pare that "such matters cannot be determined l)y sitting down and thinking, but by hard unremitting toil." Gradually, however, our knowledge of the normal functions of procreation has been expanding and a sufficient number of cases have been observed, recorded and analyzed to enable us to recognize certain factors which evidently play an important part in the etiology. Joh.v B. Deavek.J Lawson Tait originally thought that the ciliary current of the mucous membrane of the tubes and that of the uterus was in opposite direc- tions, that of the tubes being directed toward the uterus and that of the uterus moving upward, thus forming a natural meeting place of sperm and ovum at the fundus. He considered it abnormal for spermatozoa to gain an entrance into the tubes and held that impregnation occurring in the tubes through this accidental invasion of the spermatozoon was very likely to give rise to tubal pregnancy. This beautifully simple conception has yielded to the iconoclastic power of observed facts. We now know that the ciliary current of the uterus as well as that in the tubes is downward. We know that the spermatozoa can ABORTION, TUBAL (DEAVER). 189 readily, stem this current, their rate of speed being calculated by Henle as 1 cm. in three minutes. \\^e know that they quite regularly obtain entrance into the tubes and swarm up its lumen and it seems quite probable, if not certain, that impregnation in the tube is common, if not the regular method. Once fertilization has taken place develop ment begins at once. The ovum, comparable in many respects to a parasite, rapidly throws out the chori- onic villi which lay hold on the maternal tissues and by erosion secure anchorage and open up the intervillous blood spaces. Just how soon the ovum displays these grasp- ing- tendencies is unknown. The youngest ovum of which we know was discovered by Peters in the uterus of a woman who committed suicide three days after missing her period. It measured .6 x .8 x 1.3 milli- meters and was firmly implanted with numerous projecting villi in the process of formation. Certainly this ovum was less than a week old. Just what condition must be met by the maternal tissues to permit of implan- tation is uncertain. Webster is quite certain that there must be a decidual reaction and a number of observers have reported having seen decidual formation in the tubes. Normally thje oosperm is swept down into the uterus before it efifects a lodgment. The forces which accom- plish this movement are the peristalsis of the tube and the action of the cilia. Whatever delays the ovum in transit, permitting it to put out the anchoring villi, in the presence of a suitable soil, renders imminent the occurrence of an extra-uterine gestation. Analyzing 309 cases, the writer found that infection or mechanical alteration due to adhesions of the Fallopian tube predisposes to ectopic gestation. The onset of symptoms occurs as frequently at the time of an expected period or just after a nor- mal period as it does when a period is overdue. Pain, with or without bleeding, was present in every case, unless unruptured. L. K. P. Farrar (Amer. Jour, of Obstet., June, 1919). As to the nature of the soil required by the ovum we are not so certain. Concerning the influence of delay which is governed by mechanical causes everyone is agreed. These causes may be classified as : — 1. :Malformation : as diverticula, accessory ostia, and persistence of the greatly convoluted fetal contour of the tubes. 2. Obstruction from within: as in tubal polypi and torsion of the tube. 3. Obstruction from without: as in myoma and peritoneal bands and adhesions. 4. Inflammation, which acts by de- stroying the motor power of cilia and musculature and secondarily by the formation of different types of ob- struction. 5. Excessive size of the ovum itself, as in the delay which occurs in external migration of the ovum. The importance of the inflamma- tory factor in the etiology of ectopic gestation is becoming more and more appreciated and is even of use in the diagnosis, a history indicating more or less pronounced salpingitis tending to arouse our suspicions of the greater possibility of an extra-uterine preg- nancy in a doubtful case. An analysis of 170 cases in the author's clinic showed that tubal preg- nancy sometimes results from an infan- 190 ABORTION, TUBAL (DEAVER). tile condition of spiral torsion of the tubes, but chiefly from residues of old gonorrheal or inflammator}' puerperal processes. In the diagnosis inflamma- tory conditions may be dififerentiated from ectopic gestation by the leucocyte count and by puncture of the posterior vaginal wall. Fehling (Arch. f. Gynak., Bd. 92, Hft. 1, 1911). According to the site of itnplanta- tion we recognize several varieties : — 1. The interstitial, located in that part of the tube which pierces the uterine wall. 2. The isthmial. 3. The ampullar. 4. The infundibular. 5. The ovarian. These are the primary forms. Later the gestation sac by reason of rupture or growth may change its position, giving rise to the secondary forms. Thus the interstitial form may be converted into an intra-uterine by rupture into the cavity of the uterus, into an abdominal by rupture into the general cavity or into an intraliga- mentary by escape between the layers of the broad ligament. The isthmial and ampullar forms similarly may become tuboabdominal, tubo-ovarian, abdominal or intraligamentary. An infundibular or ovarian pregnancy always tends to become abdominal. The last-named condition is one of the greatest curiosities of abdominal pathology. All the undoubted cases of ovarian pregnancy so far observed can be numbered on the fingers. The interstitial and infundibular forms are almost as great rarities ; so that for practical purposes we have to do only with cases primarily isthmial or ampullar, of which the latter are most numerous, and with the forms second- ary to these primary varieties. Extra-uterine pregnancy assumes pathological significance when it undergoes ectopic attachment. The tubal ovum has a parasitic action, malignant in that it destroys maternal tissues; it embeds itself in the tube wall, and tends to the death of the mother. The growth of the ovum or the enlargement of the dead ovum mass, thinning and destroying the tube wall, leads to almost certain rupture of the tube. Primary rupture may be partial or complete and fatal. If in- complete, subsequent ruptures will be almost certain to follow. With rup- ture free hemorrhage occurs, which may prove fatal. There may be one rapid fatal hemorrhage or a series of minor hemorrhages. If death does not occur from hemorrhage, the blood and the ovum in the abdominal cavity may act as imitating foreign sub- stances which lead to loss of function and pathological changes in the vis- cera, to local or general infection, thrombosis, embolism, etc. The dead ovum is almost as harmful as the liv- ing one, from the standpoint of rup- ture, and may be more harmful as a focus of infection. C. W. Barrett (Amer. Jour, of Obstet., June, 1911). Report of a case in which the ovary was removed on account of supposed cystic enlargement. A fetus was found in it, the ovarian elements hav- ing nearly all been superseded by the intact developing ovum. W. Licbe (Monats. f. Geb. u. Gyniik., Feb., 1921). The natural outcome of extra-uter- ine pregnancy, as stated in the defini- tion, is early interruption, whether by reasons of insufficient blood supply or unfavorable mechanical conditions for the continued development of the fetus. The most common event is the formation of a tubal mole from the slow leakage of blood about the sac. This soon results in the death of the fetus and cessation of growth. In this way spontaneous recovery may ABORTION, TUBAL (DEAVER). 191 occur. I have several times in the course of pelvic operations encoun- tered old tubal hematomata which were clearly the result of a pre- vious tubal pregnancy which had terminated itself and retrogressed without giving the patient any great inconvenience. That this is not a frequent occurrence our clinical ex- perience and the infrequency of such operative findings testify. There is evidence to show that even after the death of the fetus the chorionic villi may continue to grow and exert an erosive action on the wall of the tube which, coupled with the distention due to hemorrhage, may bring about a rupture. More common than this is the gradual extrusion of the mole from the fimbriated extremity, a process known as tubal abortion. Rupture of the tube and tubal abor- tion may take place rapidly without the previous formation of a mole. These are apt to be the fulminating cases. Hemorrhage is more free in case of rupture than in abortion as a rule : more free in rupture into the general abdominal cavity than in rupture into the broad ligament, more free when the site of rupture involves the pla- cental attachment, and more free at the cornual end of the tube than at the ampullar end. [This latter tendency was tersely expressed by Formad, who used to say, "Ruptured cornual cases belong to the coroner ; rup- tured ampullar to the surgeon." Surgery in its march has modified this statement, but it still serves to point out the relative dangers. John B. Deaver.] Hemorrhage is the outcome of extra-uterine pregnancy which chiefly concerns us from a practical stand- point. It is probable that no case of ectopic gestation occurs which is not accompanied by hemorrhage at some time. It may, however, be early or late, slow or rapid, slight in amount or profuse. It is the chief, though not the only, factor in the production of so-called shock, and is the main agent in a fatal outcome. I shall have more to say concerning hemor- rhage under the question of treat- in ent. If the patient be fortunate enough to survive the primary rupture and the fetus live, she still has to face the possibility of a second rupture of the gestation sac in its new position. Occasionally an extra-uterine preg- nancy may progress to term. Usually this is rendered possible by the escape of the fetus within its amniotic sac into the general abdominal cavity, the placenta remaining attached at the primary site. In this event, after a spurious labor at term, the fetus dies and offers an inviting site for in- fection. [Operation is here indicated on the same principle as in the case of any foreign body which threatens the host. This holds true in spite of the well-known fact that in some instances the fetus has caused little harm, being converted into a lithopedion or adi- pocere. Such a late terminal event presup- poses a series of diagnostic failures which we trust, now that the condition is so well known and understood, may not come to pass. John B. Deaver.] TREATMENT.— This involves a discussion of the immediate consider- ations concerning an active rcrsiis expectant mode of treatment in cases of rupture. [It has long been my practice to operate every acute case of extra-uterine pregnancy without delay and my results have been so uniformly good that it would never have occurred to me to reopen the question. Robb, in 1907, came forward with the as- 192 ABORTION, TUBAL (DEAVER). sertion that surgeons were losing many of their desperate cases from overhaste in operating during shock. He believes that shock is mainly due to the effect of the acci- dent of rupture upon the nervous system, that it would be a great rarity for a patient to bleed to death and that cases in which the loss of blood in itself would be sufficient to bring about a fatal termination would seldom be seen in time to save the patient. He bolsters his position by animal experi- ments, having observed that dogs do not die of hemorrhage even after section of the uterine and ovarian vessels. Just what he considers the cause of death in these cases is not clear. The coroner's statistics of Dr. Formad, though he admits that it is on record that in certain instances the amount of blood which was found was enough to fill the abdominal cavity, Robb dismisses by saying that "such statements are entirely too meager to give us any def- inite knowledge, nor can they be entirely depended on." He also says in this regard that "in a given fatal case it must also be proven that there were no other and possibly equally important factors in the causation of the fatal result." He not only doubts that the coroner saw the blood, but he invites us to prove that the patient did not die of cere- bral apoplexy instead of abdominal hemor- rhage. As for the animal experiments I can only say that, if he has not seen a woman die from hemorrhage from a uterine artery, he has been more fortunate than I have been, and that I therefore still resort to the old- fashioned expedient of tying as secure a knot about that vessel as I am able. John B. Deaver.] Formerly it was not such an un- common thing for these patients to bleed to death. Of the 500 cases reported by Parry there were 336 deaths, 174 of which were from rupture and hemorrhage. Of 113 of these in which the time of death was stated 81 had died at the end of 24 hours and at the end of 48 hours only 15 were left alive. Of course this gives a greatly ex- aggerated idea of the danger because in those days only the evident and severe cases were noted. Still it serves to show that, without opera- tion, death, which was shown by autopsy to be associated with exces- sive hemorrhage, was not so un- common a sequel. If these deaths were not due to hemorrhage, what did cause them? [Has anyone seen a death from shock of rupture with an, insignificant or even a mod- erate amount of blood in the peritoneal cav- ity? In the cases which I have seen in this so-called state of shock, the condition of the patient bore a striking parallelism with the amount of blood found in the abdominal cavity. I wish to enter a strong protest against the loose use of the term shock in this condition as well as the vicious tendency of such flashy phrases as "adding shock to shock. John B. Deaver.] The great danger in these cases is not from the shock of rupture, but from the subsequent hemorrhage. Or, to be very conservative, severe hemorrhage is necessary to produce the fatal outcome. Let us consider for a moment this factor, shock. It is known that any acute lesion of the peritoneum produces, through shock to the great abdominal nerve centers, a certain train of symptoms, whether the lesion be due to rupture of the appendix, twisted pedicle of an ova- rian tumor, passage of gall-stones, acute strangulation of the intestine, or rupture of an extra-uterine preg- nancy, and to this train of symptoms Gubler has given the name "perito- nism." These symptoms are inde- pendent of inflammation or of septic intoxication. They are : pain, pro- found exhaustion, distressful anxiety, pallor; soft, quick pulse : cold extremi- ties, shallow respiration, nausea and vomiting. These vary in degree and are common in some degree to all cases in which there has been a wide ABORTION, TUBAL (DEAVER), 193 and abrupt impression upon the nerve centers of the abdomen. This is the train of symptoms which follow im- mediately upon an acute rupture of the gestation sac and gives the picture properly denominated as shock. This shock as such is practically never fatal. Chnical evidence is conclusive on this point. We do not find our patients dropping over dead from acute strangulation, twisted pedicles or tubal ruptures. The shock exerts its maximum influence at the moment of the tearing injury to the perito- neum and sympathetic trunks and practically ceases at once with the release of tension after the laceration has been effected. This factor is sudden, momentary, expends its energy and ceases. Reaction begins, or would begin at once, either spon- taneously or with the aid of stimu- lants. This sudden insult to the peritoneum and the great sympathetic centers is not what places the patient's life in jeopardy and holds her hover- ing in the balance for hours. This is but the advance agent of the real executioner, hemorrhage. Read in the same order as before, leaving off the pain in the beginning, we have in the symptoms of shock the symptomatology of hemorrhage : Pro- found exhaustion, distressful anxiety, pallor; soft, quick pulse; cold extrem- ities, shallow respiration, air hunger, nausea and vomiting. [Who is that man who will tell us in these cases where shock leaves off and hemor- rhage begins to play the leading role ? I feel most strongly that we are dealing here with a wrong use of words, that there is a sophistical "nigger in the woodpile." I do not believe that the patients reported by the advocates of the expectant treatment as suf- fering from shock were suffering from pri- mary shock, but instead from shock plus 1—13 hemorrhage, and that, by the time they were seen by the surgeon, that hemorrhage was playing by far the chief role. Those patients who are fortunate enough to lose but a small quantity of blood at the time of rup- ture react from the shock with considerable promptitude. By the time proper surgical intervention can be brought to bear, their condition is such as to give the surgeon little immediate anxiety as far as the shock of operation is concerned. These patients should be operated at once on account of the danger of secondary rupture or a re- newal of bleeding. They should all get well. John B. Deaveu.] An immediate operation detracts nothing from the chances, but guards against imminent danger. Those patients who, when seen an hour or several hour^ after rupture (I am speaking of conditions as we find them, for patients do not come to a hospital or doctor's office to be handy at the time of rupture), are hanging in the balance with the symptoms some are pleased to call shock are not suffering from shock, but rather of shock plus hemorrhage, shock in small type, hemorrhage in large red capitals, and the examples of reaction are not proofs of the wisdom of wait- ing, but of the fact that many desper- ate cases will stop just short of bleed- ing to death if left to themselves, a fact which has for years been patent to all. After operation for tubal pregnancy patients became again pregnant in 35.19 per cent, of the cases, but only 18.5 per cent, of these are extra- uterine. Out of 4526 cases of tubal pregnancy a recurrence was reported in 4.68 per cent. H. A. Dietrich (Zentralbl. f. Gynak., Apr. 9, 1921). There are certain factors which would favor the cessation of bleeding, such as a long and voluminous sig- moid or omentum wedging down in the pelvis, but, as we are not often 194 ABORTION, TUBAL (DEAVER). furnished with a diagram of interior arrangements in these cases, we do not know whether these stanch allies are on the ground. The character of the rent and tlie coagulability of the blood we cannot estimate. [As sure as there are immutable laws of hydrostatics and of the circulation of the blood, these patients have died in the past in considerable numbers from hemorrhage and occasionally die today from that cause, and the only reason more do not die of it is be- cause of the early operation practised by clinical surgeons. I am willing to grant that a patient should not have a "penknife" operation done on her before she has recovered from her first faint. There is reason in all things. It is equally true that a patient in articulo mortis should not be subjected to operation. "The re- sources of surgery arc rarely successful when practised on the dying. These princi- ples, however, should not be made use of to attack a mode of treatment which has been crowned with the highest success." John B. Deaver.] The treatment of unruptured ec- topic is operative as soon as the diagnosis has been made. After rupture has taken place, operation should be postponed until the patient has recovered from the shock inci- dent to the hemorrhage following rupture. Almost all of these patients will "come back" with rest and mor- phine. They are given an initial dose of y2 grain (0.03 Gm.) of morphine, followed by % grain (0.016 Gm.) every 3 hours until the respirations are reduced to from eight to twelve per minute. The writer has yet to see a case which has not reacted and become a safe operable risk under this treatment. The operation is always done by the abdominal route and the tube either emptied of its contents or am- putated. In the removal of the tube great care should be exercised in in- dividually ligating the vessels in the mesosalpinx so that the collateral circulation to the ovary is not inter- fered with. "After the tube is re- moved, the ovary is suspended by suture of the infundibulopelvic liga- ment to the round ligament and the raw surface at the top of the broad ligament peritonealized by whipping the mesosalpinx and round ligament together. J. O. Polak (L. I. Med. Jour., xii. 121, 1918). My position then is this: A con- tinuance of the collapsed condition, commonly, and as I believe erron- eously, termed shock, for a longer time than one hour indicates tliat a considerable hemorrhage has oc- curred and may be continuing. The surgical indications are clear — stop the bleeding; stimulate. Let us not revert to the dark ages in the ranks of those who "watched the life ebb rapidly from the pale victim of this accident, but never raised a hand to help her." According to Schauta, the maternal mortality in non-operative cases is 68.8 per cent. The writer is inclined to feel that this percentage is too high, that more cases of ectopic gestation escape recognition and live than we have sus- pected. At the Columbus Hospital op- eration is alwaj'S resorted to, and, per- formed speedily and promptly, should not give a mortality of over 2 per cent. The dangers are from shock, hemor- rhage, sepsis, exhaustion, and intestinal obstruction. J. M. Keyes (N. Y. Med. Jour., Aug. 6, 1910). Since 1900 I have had 110 cases of extra-uterine pregnancy, many of them of the acute type, without a death. My procedure in these urgent cases is as follows: If the condition be very low, stimulation is begun on admission by hypodermoclysis and strychnine. If there is extreme rest- lessness, morphine is a valuable ad- junct administered, of course, with due discretion. cr -t (T) CTQ 3 P o d I n ABORTION, TUBAL (DEAVER). 195 They are placed on the table with as Httle disturbance as possible and a light quick etherization given. Prep- aration is rapidly completed and intravenous transfusion of normal saline solution started as the abdom- inal incision is made. "Get in quickly, o-et out quicker" applies here as forci- ly as anywhere in surgery. The nfifending tube and ovary are re- moved. The clots are scooped out, and, if the condition of the patient warrants, the abdomen is flushed out md filled with normal saline before closure. The writer divides ectopic gesta- tions into 4 groups, viz., with neg- Hgible, moderate, severe, and fatal hemorrhage. Patients of the first group frequently recover spontane- ously. If the hemorrhage is discov- ered, the operation can be deferred until the peritoneal irritation sub- sides. In the third group, shock is great. The pain should be relieved by morphine, the head lowered, and the extremities bandaged. A donor should be procured for a blood trans- fusion, which is to be started before the incision is made in the abdomen. The fourth group of cases bear trans- portation poorly. Infusing these pa- tients with saline solution to which 6 per cent, gum acacia has been added will restore the circulation until the patient can be taken to the hospital. Hermann Grad (Trans. N. Y. Acad, of Med.; Med. Rec, Dec. 4, 1920;. I have frequently seen the patient go ofif the table with a far stronger pulse and in better condition than before the operation, a sufficient ref- utation of the charge of "adding shock to shock." I have rather re- fused to allow hemorrhage to be added to hemorrhage, and now I am not afraid to fill her vessels with suffi- cient fluid to satisfy the mechanical needs of the circulation. [My last case before this article was writ- ten happened to be most appropriate to this discussion : A young woman, aged 24, mar- ried three years, with nothing of note in her past history. She had had one child nine months ago, which died in January. No miscarriages. Menstruation had always been regular and normal up to her January period, which she missed. At the February period she bled quite profusely and for a longer time than usual. No staining since. Suddenly at 6 a.m. on February 12th, dur- ing coitus, she had an acute pain in the lower left side of the abdomen, followed in a few minutes by syncope. Soon she recovered, but fainted several times in the course of the morning, and vomited several times. Grad- ually grew weaker and grew short of breath. On examination she did not have a particle of color in her skin or lips. Expression was anxious : she was restless and dyspneic. The pulse was about 180 and barely per- ceptible. Her abdomen was moderately dis- tended and tender in left side low down. Vaginal examination was negative except for tenderness in the left lateral fornix. She was taken to the operating room and subcutaneous infusion started with the ether. Preparation having been quickly accom- plished, the operation and intravenous trans- fusion were started together. A left-sided tubal pregnancy (see colored plate) the size of a hickory nut was found in the isthmial portion about 2 cm. from the cornual ex- tremity. Through the tube was a perfora- tion only about as large as a pinhead. No time was wasted in determining whether there was any active bleeding. Tube and ovary were removed. As the patient's con- dition was improving on the table, I washed out the blood, of which there was a large quantity, and filled the abdomen before clos- ure with salt solution. Her pulse, which before the operation was 180, at the end of the operation was 140 and much improved in quality. She was put back in bed and continuous proctoclysis started. John B. Deaver.] I wish to call attention to the value or rather necessity of filling the empty blood-vessels with saline in these depleted cases. In the above case, the amounts used were as fol- lows: By hypodermoclysis at the 196 ABSCESS (WITHERSTINE). beginning. 1000 c.c. Intravenous transfusion during the operation 2000 c.c. Left in the abdomen at least 1500 c.c. Then in the twelve hours after operation her thirsty vessels absorbed by way of the large bowel 4000 c.c. additional. Nearly nine liters of saline, over two gallons of fluid to meet the mechanical needs of the circulation. Without this saline my patient would liave run grave danger of dying on the talile. As the intra-abdominal pressure is released by incision the blood flows into the "splanchnic tank" and from the great depiction due to hemorrhage nothing is left in the great vessels for the heart to pump. The medullary vessels are asphyxiated and death results. This restoration of the fluid volume of tlie blood is a most impor- tant point. In 12 out of 135 operative cases of extra-uterine pregnancy, the writer reinfused into a vein 300 to 1000 c.c. of the woman's own blood, diluted with an equal amount of physiologic salt solution with a little sodium citrate. Tiie blood was scooped or soaked up from the abdominal cavity, passed through a funnel over some gauze as a filter, and then into a receptacle containing salt solution. One woman died of peritonitis — the only death in 12 cases. Von Arnim (Zentralbl. f. Gynak., Nov. 29, 1919). The writer has likewise had good results from reinfusion of blood in tubal abortion or rupture of the spleen. He punctures the abdominal wall in the lower third of the rectus muscle and aspirates, to confirm the presence of fluid blood. The infusion tube is introduced into the vein by the assistant as the abdomen is being opened. The parietal peritoneum is then drawn up into a cone and the blood around the bladder runs out. From one-half to 1 liter of fluid blood is thus secured in a few minutes. strained, citrated and poured into the infusion funnel. Kulenkampff (Zen- tralbl. f. Gynak., Apr. 17, 1920). John B. Deaver, Philadelphia. ABSCESS.— DEFINITION.— A circumscribed collection of pus in an adventitious cavity, the result of local- ized inflammation due to infection by ]nis-forming microbes, differing from diffuse suppuration which is not cir- cumscribed and from purulent effusion or empyema which is found in a natural or pre-existing cavity, as the pleura, pericardiimi. mastoid cells, etc. VARIETIES.— An abscess may be acute, or warm, when due to pus- microbes only: staphylococci, strepto- cocci, and others; chronic, or cold, when due to a specific microbe, especially that of tuberculosis. Abscesses have been classified ac- cording to : — 1. Etiology. — Atheromatous, em- bolic, fecal (stercoraceous), metastatic, miliary, ossifluent, puerperal, pyemic, lesidual, symptomatic or congestive, tropical, tubercular (strumous, lym- phatic, or scrofulous), etc. 2. Pathology. — Acute or warm, canalicular, caseous, chronic or cold, critical, gangrenous (anthrax), lig- neous, perforating, phlegmonous, etc. 3. Location (Organ or Tissue In- volved).— Alveolar (gum, jaw, teeth), of axilla, bone (subperiosteal), brain (cerebral, cerebellar), bursal, corneal (hypopyon), deep, dorsal, follicular, hepatic, of hip-joint, iliac, ischiorectal, lacunar, lumbar, mainmary (milk, weid or weed, breast), marginal, mediastinal, meningeal (extradural, subdural), of neck, nephritic and perinephritic. of nose, of palate, palmar, of pancreas, perityphlitic, popliteal, of prostate, psoas, rectal, retropharyngeal, of skin ABSCESS (WITHERSTINE). 197 (furunculosis), of scalp, of space of Retzius (preperitoneal cavity), spinal or vertebral, of spleen, superficial, thecal, urethral and periurethral, vulvo- vaginal (Bartholinian), etc. All the above varieties will be considered under their respective anatomical heads. ACUTE, OR WARM.— Symptoms. — An acute abscess may be either su- perficial or deep. When it is superficial the local symptoms predominate ; when it is deep the general symptoms are more marked. The pain, due to compression of the nerves by the disturbed tissues, varies in degree with the density of the parts involved, the local supply of sensitive nerves, and the tension produced by the inflammatory products. In superficial abscess the pain is generally localized in the center of the swelling, and is sharp and lancinating; in deep abscess it is more diffuse and dull. Redness is due to engorgement of the local blood-supply, and the swelling to the inordinate distention of the ves- sels and the secondary escape of blood- plasma, colorless corpuscles, etc., into surrounding tissues. It may become very great in certain regions, such as the lids, the lips, etc., in which the cellular tissue is lax. As the purulent foci run together and form a single cavity, the center of the tumefaction becomes soft, and darker in color, and the abscess is said to be "pointing." Edematous infiltration in superficial abscess denotes the presence of pus ; in deep abscess subcellular edematous in- filtration is an important sign of deep suppuration. Local heat, throbbing, and tension are mechanical results of the causes of tu- mefaction tending to decrease as the formation of pus progresses. Hyperpyrexia is in relation with the location of the abscess, the ease with which the pus-microbes can enter the circulation, and the amount of pus and necrotic tissues present. In superficial abscess there is but little rise of tem- perature, but in deep abscesses it some- times reaches 104° F. (40° C.) at the time the wall of granulation tissue is established. A remission of about one degree each morning usually takes place. When the pus has found an issue, or has become completely sur- rounded by the limiting membrane, the intensity of the fever is usually reduced. In a superficial abscess, if a chill oc- cur, it is usually very slight, and ap- pears between the fourth and the eighth day. It indicates the formation of pus. In a deep abscess a chill generally occurs, lasting from a few moments to half an hour. Fluctuation is generally obtained when the purulent focus has been formed. A sharp localized pain on pressure over the apex of the swelling obtained at this time supports the likeli- hood that pus is present, but fluctua- tion is liable to be a misleading symptom. Interference with motion or the normal functions of a part is sometimes produced through the proximity of an abscess. In deep-seated abscess any or all of the general symptoms of abscess may be lacking, except loss of flesh and strength. This is especially true of hepatic or cerebral abscess. The symp- toms usually present are local tender- ness and pain, pressure symptoms, overlying edema, brawniness, muscular rigidity and ankylosis of neighboring joints, in addition to the symptoms of acute suppuration — fever, chills, sweats, anorexia, restlessness, etc. 198 ABSCESS (WITHERSTINE). Etiology. — Inflammation due to trau- matisms and lesions of all kinds, espe- cially the introduction of foreign bodies under the epidermis, are the usual causes of abscess. While blows do not apparently produce superficial lesions in the majority of cases, the fact remains that an invisible abrasion may be present and serve as a channel for the introduction of the pyogenic organ- ism. The cutaneous glands, through weakened local resistance, may also become the transmitting media. Any cause removing the epithelial layer of the mucous membrane may also form the primary etiological factor of an abscess in the membrane or in the sub- mucous connective tissue. Abscesses also arise in connection with the various septic fevers. The writer refers to 2 cases of inflamniatorj- nevv<^ro\vths of ex- tremely slow development which had led to the diagnosis of cancer. They were hard and located in the ab- domen in both instances. The pa- tients were men of 26 and 72. The tumors were observed 4 j'ears and 3 months, respectively, and both were permanently cured by clearing out the focus. There was a history of operative treatment for inguinal her- nia not long before in each case, but in the younger man unsuspected ap- pendicitis was probaldy the main fac- tor. In both cases only the ordinary pyogenic germs were found. Filardi (Policlinico, Aug., Surg. Sect.. 1917). The three essentials in the formation of an abscess are : pyogenic organisms in sufficient numbers and virulence, their proper implantation within the tissues, and a sufficiently low resisting power, either local or general. Pathology. — While several varieties of micro-organisms are found in the pus of an acute abscess, the principal ones which ordinarily cause purulent inflammation are the Staphylococcus pyogenes (aureus and albiis). Strepto- coccus pyogenes, Micrococcus gonor- rhccce, Bacterium coli commune, Bac- terium, pyocyaneum, pneumococcus, and the Sarcina tetragena. Less frequent in the production of suppuration are the typhoid bacillus, the influenza bacillus, the diphtheria bacillus, the actinomyces, etc. An acid-fast bacillus was culti- vated by the writer from chronic in- tractable pustules covering the back, buttocks, and thigh of a soldier re- turned from France. Xo micro- organisms were seen in the pus, and none could, at first, be cultivated from it. But subsequently there was grown, on more than one occasion, the acid-fast bacillus referred to. Cobbett (Brit. Med. Jour., Aug. 17, 1918). According to Kreibich suppuration can occur in man without the presence of ))acteria. Both in animals and in man, suppuration may be due to the irritation of chemicals. Investigators have shown that suppuration is only a certain stage of inflammation, not a separate qualitative form of inflamma- tion. The serous formation of blebs and l^ullre becomes purulent without the presence of bacteria. Chronic suppurative processes are, according to Lyman Allen, very fre- (juently unattended by fever, while acute suppurative processes are fre- quently unattended by fever. In a given case, therefore, the absence of fever must have little \veig"ht by itself in excluding the possibility of suppu- ration. Since a rise of temperature above 100° F. occurs in about two- thirds of all aseptic cases, the pres- ence of fever alone must have little weight in making a diagnosis of sup- puration. Suppuration is almost invariably {)re- ceded by inflammation due to the ABSCESS (WITHERSTINE). 199 pyogenic micro-organisms. The first effect of the bacterial toxins on the local circulation is to cause an increased rapidity of the flow of blood in the part, the vessels becoming engorged and dilated. This is succeeded by slowing of the current and passage through the vascular walls and into the surrounding tissues of colorless corpuscles (leuco- cytes), a few red corpuscles, and blood- plasma, the latter of which become coagulated and finally softened. One or several cavities are thus formed ; but, if the cavities are multiple, the barriers usually soften and a single focus is established. The pus is composed of the corpuscles which perish in the cavity thus formed, the broken-down remains of tissue, and the plasma. At a distance from the location of the abscess the circulation is normal, but, as the diseased area is approached, the slowing of the blood-current becomes gradually more evident, until a zone of living leucocytes is met, forming a pro- tective barrier around the abscess cavity. The surrounding parts also become permeated with new vessels, and a zone of granulation tissue (the pyogenic membrane of older writers) is formed. The spread of the suppuration being thus checked, the pus is forced to the surface because it finds the least resistance in that direction ; but, if an aponeurosis or fascia interfere, it bur- rows until an exit is found. The role of the wliite corpuscles (leu- cocytes) has been interpreted in various ways ; Cohnheim considered them as elements of repair; others have attrib- uted to them tlie role of scavengers. The accepted theory at present, how- ever, is that of Metchnikoff, who con- siders them able to attack and destroy invading organisms. The process is termed by him phagocytosis, the cells being called phagocytes (<^ayto, to eat, and KUTos, a cell). The dead leucocytes in pus must be looked upon as the cells that have been brought up rapidly to interfere with the spread or diffusion of the products of the micro-organisms ; a large number of these cells coming in contact with the poison in a concentrated form may succumb to its action ; but before doing so they are able to deal with a certain quantity of the poisonous material, breaking it down and rendering it inert. Other cells are constantly being brought up to assist these, until, at length, the bacteria are completely hemmed in. They live for a short time on the dead tissues ; but, being localized by the barrier of leucocytes, they ultimately die, either from inanition or because they are poisoned by their own prod- ucts or by immunizing constituents of the blood-plasma. It is found very frequently on opening an abscess that no organisms can be seen, those that were originally present appearing to have undergone degenerative changes and to have been taken up by the phag- ocytes, or devouring cells. The process includes, according to Sajous, participation of the proteolytic or peptonizing action of enzymes in the serum supplied in large quantities to the abscess. The prevailing view is that these are produced by the pyogenic bacteria. From his viewpoint (see "Internal Secretions," vol. ii, 4th ed., 1911, p. 907) these ferments are se- creted (though originally derived from the pancreas, thyroid, and adrenals) by phagocytes (]\Ietchnikoff's trypsic cy- tase), themselves and their liquefying action has for its purpose to destroy the bacteria and their toxins in the ab- scess. The pathogenic organisms are first sensitized and softened by opso- 200 ABSCESS (WITHERSTINE). nins and agglutinins (thyroid secre- tion), and thus rendered vuhierable not only to the digestive action of the phag- ocytes when ingested by these cells, but to the ferments (trypsin mainly) they contribute to the abscess fluids, in which they accumulate in large numbers. Differential Diagnosis. — Fluctua- tion only indicating the presence of fluid, the presence of this sign without the other symptoms mentioned should inspire great circumspection, especially if surgical measures are employed. Aneurism is the most dangerous con- dition to fear. It has. however, a less acute history, a peculiar thrill and ex- pansile pulsation, and can only exist in close proximity to a large vessel. Certain semisolid growths may sim- ulate an abscess. When the possibility of an aneurism has been eliminated, a fine trocar or exploring needle, if care- fully used, will determine the diagnosis. Prognosis. — This depends upon the general health of the patient. In the robust a suppurative process usually reaches the stage of resolution without giving rise to complications. In indi- viduals weakened by disease, hereditary or acquired, an abscess may be pro- tracted and exhaustive, and diffusion is more likely to occur if resisting tissues interfere with the superficial evacuation of the pus. Deep abscesses are espe- cially prone to become protracted through this cause, the resistance of muscular aponeuroses, etc., forcing the pus into the cellular interstices. Fistu- lous tracts, or large suppurative areas, are thus created, and the patient may succumb to blood poisoning or its con- sequences. Treatment. — General Measures. — Rest and elevation of the affected region, if possible; salines, if purgation is necessary. Easily assimilable food, but not low diet ; avoidance of stimu- lating beverages, alcohol, coffee, etc. Internal Remedies. — If the case is seen early the suppuration can some- times be arrested by the use of one of the following agents, supplemented by one of the local applications: Tincture of aconite, 3 to 10 drops every hour, closely watching the patient's pulse ; tincture of veratrum viride, 1 drop every hour until the pulse becomes slower, the skin moist, and slight nausea occurs ; or calcium sulphide (sulphurated lime), Yio grain every hour; or, again, R Sulphate of quinine, 1 grain. Ext. of nux vomica, Y^ grain. P'or one pill, to be taken every three hours. Many incipient abscesses disappear under the internal use of the hypophos- phites of ix)tassium, sodium, and cal- cium. They also act as an excellent prophylactic, if given before pus has formed. Tousey believes them to be more efficient than calcium sulphide. The combination used by Tousey is 5 grains of calcium hypophosphite, and 2 grains each of the sodium and potas- sium hypophosphites, administered in syrup or two capsules, followed by half a glassful of cold water. Fresh brewers' yeast in doses of 3j to oij in water or undiluted, just before or during meals, is a favorite remedy with many, although diarrhea some- times results, even when the yeast is fresh. A substitute preparation is inade by macerating compressed yeast in water. Desiccated veast is also used. In addition to these internal remedies, we should not forget that stimulation, nutrition and general hygienic measures are of considerable value. Thyroid gland in doses of 1 or 2 grains three times daily hastens the disappearance of abscesses, by increas- ABSCESS (WITHERSTINE). 201 ing the proportion of opsonins in the blood (Sajous). Ferges and Gergo recommend the use of fresh normal blood-serum from the horse or from cattle in the local treatment of acute suppurative proc- esses in 100 cases. The pus was first aspirated, serum next 'injected to rinse out the cavity, using a needle closed at the end, but with a row of openings just above it ; then the excess of fluid aspirated, and the opening covered with a bit of sterile gauze held by ad- hesive. It is important that all the excess of serum be removed from the cavity ; otherwise, symptoms of serum intoxication may follow. The serum apparently produces both a passive and an active immunity, stimulating leucocytosis and phagocytosis. Bet- ter healing can be obtained by this method, according to the authors, than in any other way. Acute abscesses in the soft parts, whatever be the micro-organism present, show espe- cially good results. (3ne treatment with the serum generally suffices. External Remedies. — The surface is carefully cleansed with antiseptic soap and sprayed with a 2 per cent, carbolic acid solution, or with hydrogen per- oxide, every two hours, the atomizer being used for ten minutes at each sit- ting. (Verneuil.) Compresses dipped in hot 1 : 4000 corrosive sublimate solution are very effective. If abscess is upon an ex- tremity, a 1 : 4000 corrosive sublimate solution may be employed as a bath for the limb, the latter being left i m the solution several hours at a time. A solution of nitrate of silver (30 grains to the ounce) may be applied frequently with a camel's hair pencil. Tincture of iodine may be applied in the same manner every three hours. \\'hen the surface becomes very tender, belladonna ointment may be rubbed in every two hours. In abscesses characterized by very severe pain a 10 per cent, solution of cocaine may be introduced by cata- phoresis, the anode sponge of a gal- vanic battery being applied to the part. The sittings should last five minutes, and be repeated every three hours, the current not exceeding 5 milliamperes. During the intervals warm fomenta- tions— with borated. camphorated, or pure water — are of great value. Encouraging results obtained in the treatment of tendon-sheath phlegmons and suppurating inflammation in gen- eral with superheated air, applied with an ordinary apparatus. It is used twice a day for two or three hours each time, maintaining a temperature of from 90° to 110° C. (194° to 230° F.V within the frame at half its height. Thus ar- ranged, the temperature on the skin averaged 44° or 47° C. (111° or 116° F. ), and the acceleration and sweating induced seemed to keep the temperature of the skin within due bounds. The ap- plications of the hot air are made the day after the abscess has been incised and evacuated, and the cavity packed with iodoform gauze. He also states that neglected injuries of the fingers which would otherwise have necessi- tated amputation healed under this hot-air treatment without requiring operative measures, and recovery was hastened. This treatment also caused an abolition of pain. (Zentralblatt fur Chir., Oct. 24, 1908.) Pads of gauze wrung out of hot boric acid solution (an ounce to a quart of water), applied as hot as the patient can bear them, and well covered with oiled silk to keep in the heat and mois- ture, are the best; wherever applicable, as with the hands or feet, the inflamed part should preferably be submerged every hour for a period of five to ten minutes in the hot boric solution itself. 202 ABSCESS (WITHERSTINE). The application of a sheet of zinc, the thinnest possible, cut to tit the shape of the, lesion and applied di- rectly to it, was found exceptionally effectual by the writer, who attrib- utes the results to the ions gener- ated by the different nascent com- pounds'of zinc. The metal is held in place with a dressing which is left undisturbed for 5 or 7 days. Any tendency to hypertrophy of the edges of the lesion calls for cauteri- zation. Long rebellious cold ab- scesses yielded promptly to this measure. C. H. Sztark (Arch, de Med. des Enfants, Oct., 1918). Wright's Bacterial Vaccines. — Treatment of staphylococcus and strep- tococcus infections (abscess, suppura- tion, etc.) by the therapeutic inoculation of staphylococcus and streptococcus vaccines, as suggested and developed by Sir A. E. Wright, of London, has found many endorsers. A bacterial vaccine is a sterilized, standardized emulsion of the infecting micro-organ- ism. It is made by scraping the film of a recent agar culture into a 1 per cent, salt solution, sterilizing at 60° C. (140° F.), and subsequently standardizing to a given nuinber of micro-organisms per cubic centimeter. The method is, how- ever, a new and complex one, and, until its use has been more thoroughly ex- plored, it should only be employed under the guidance of an expert. Whether an opsonic control of the in- jections will always be necessary still remains to be shown, but in all cases the use of the vaccines should be pre- ceded by a most careful bacteriological examination, and the particular vaccine should be prepared for each individual patient. The dose of staphylococcus vaccine is 100 to 1000 millions; an inoculation being made every ten days. The dose of streptococcus vaccine which is more toxic than staphylococ- cus is 20 to 60 millions ; the inoculations being repeated weekly or every two or three weeks. Case of furunculosis, subperiosteal abscess of the head, and necrosis of the bones of the skull treated by oper- ation and autogenous vaccine. Staphy- lococcus aureus was recovered from the parietal abscess and from the blood. An autogenous vaccine was made, and 4 doses were given at intervals of four days. The first dose was 50,000,000. the second 100,0a),000, and the last 2 150.000,000. With no constitutional re- action, the local condition rapidly im- proved. The general condition of the patient improved, but a portion of the bone at the base of the abscess was denuded and necrosed. At a later date this sequestrum was removed and the I)aticnt was given 3 more injections of the autogenous vaccine at four days' interval, each dose being 150,000,000. Within three weeks the patient was in normal condition. The author urges preference for the autogenous vaccine. G. G. Ross (Monthly Cycle, and Med. Bull., Sept., 1910). Bier's hyperemic treatment (passive congestion or artificial hyperemia) of acute abscesses has given excellent results as to immediate relief of pain and reduction of inflammation. Inflammation, according to Bier, does not in itself represent a diseased condi- tion, l)ut is a phenomenon indicating the body's attempt to resist a deleterious invasion. To increase this beneficent inflammatory hyperemia resulting from the fight of the living body against in- vasion, is the aim of Bier's Itypereinic treatment. The blood must, however, continue to circulate; there must never be a stasis of the blood. Bier's method artificially increases the redness, heat, and swelling, three of the four symp- toms of acute inflammation. He dis- cards all means that tend to subdue inflammation. Bier produces this hyperemia by any ABSCESS (WITHERSTINE). 203 or all of three methods : Elastic band- age or band, cupping glasses, and hot air. In the use of the elastic bandage, it should cause slight obstruction to the return of the blood, but not sufficiently- firm as to obliterate the pulse beat below or be in the least way annoyable to the patient. The technique is correct if there is absolutely ho increase of pain, and if there is visible hyperemia of the parts subjected to treatment; the portion distal to the bandage must appear bluish or bluish red — never white. All dress- ings should be removed while the com- pressing elastic bandage is in place, the wounds or bruises being covered with sterile gauze kept in place by a loosely applied towel. Under hyperemic treat- ment any abscess must be opened and pus evacuated. Acute inflammatory processes require application of the hyperemic treatment for twenty to twenty-four hours per day. In chronic cases, especially if tuberculous, shorter sittings, from two to four hours per day. In the use of suction apparatus or cupping glasses to produce obstructive hyperemia, the skin should turn red or bluish red, but never white ; circulation must not be interrupted. The vacuum apparatus of large size is supplied with a suction pump. These suction glasses are applied for five minutes, six times daily, with intervals of three minutes between applications, in order to give the edema and hyperemic swell- ing an opportunity to disappear. Thus the entire time of treatment is three- quarters of an hour each day. Treatment of acute abscess by passive congestion has given excellent results. Cases of purulent arthritis, suppuration of tendon sheaths, and acute abscesses and carbuncles have shown without ex- ception almost immediate relief of pain and reduction of inflammation. The ab- scess either became "cold" or its con- tents changed to serum or were re- sorbed. Purulent arthritis was treated with passive motion after all pain had been relieved. The writer selected 15 of the 110 cases cited for brief descrip- tion in the article. All cases were quickly cured, and it was only rarely necessary to open the abscess. Of the 15 cases reported, 8 were resolved, 3 were opened, and 4 were discharging when admitted. Bier (Miinch. med. Woch., Jan. 31, 1905). By means of artificial hyperemia we can often abort an infective process and save the breaking down of tissue, or, if at the beginning of treatment the proc- ess has gone on to the breaking down of tissues, the hyperemic method assists in quickening the process of expulsion of the products of infection and also the process of repair. J. H. Beaty (Jour. Minn. State Med. Assoc, Jan. 15, 1908). In the use of hot air to produce hyperemia we produce an arterial hyperemia which differs from the ob- struction or venous hyperemia. The effect of hot-air hyperemia is also dif- ferent upon the body and also upon the pathologic process. This last method is apparently not used in the treatment of abscess. The author comments on the value of Wright's solution of sodium chlo- ride, 4 per cent., and sodium citrate, 1 per cent., as an agent for promot- ing drainage of abscesses. The hy- pertonic solution of sodium chloride by osmosis brings about a flow of lymph through the abscess walls, while the sodium citrate, by precipi- tating the calcium salts in the lymph, prevents the latter from clotting, and thus perpetuates the discharge. The lymph and 4 per cent, salt solution both antagonize the bacteria. The technique of treating an abscess by this plan is described as follows: The abscess is opened by a wound as small as will allow the cavity to be wiped out, or thoroughly emptied by 204 ABSCESS (WITHERSTINE). expression. The surrounding skin is well cleaned with 70 per cent, alcohol and smeared up to the very mouth of the wound with boric acid or euca- lyptus vaselin, in order to avoid skin irritation from the salt solution. If the skin tension closes the opening a bit of rubber dam may be put in. The wound is covered with a volumi- nous pad of gauze or of absorbent cotton covered with gauze, dripping wet with hot salt and citrate solu- tion. A many-tailed bandage or some other application holds the poultice in position, and the part is put at rest. Outside the dressing may be applied a hot flaxseed poultice or a hot-water bottle. In any case, as often as the dressing gets cold, more of the hdt solution is poured over the whole dressing to wet and warm it again, or the, dressing is removed and the whole part soaked, if possible, or bathed with the same solution. The solution is contraindicated if there is a tendency to persistent ooz- ing of blood from the wound, and where the formation of protective adhesions is dcsiraljle. Inguinal and axillary bubo, abscess of neck, septic fingers, mastoid wounds, otitis media after paracen- tesis, all drain well under this method. The solution should be used only for the first thirty-six to seventy-two hours after operation, during the acute stage of inflammation. The wound is then filled with glycerin or balsam of Peru. Crandon (Annals of Surg., Oct., 1910). The iodoform bone-wax recom- mended by von Mosetig-Moorhof tried in 5 cases, in which the wax failed and was discharged. It is of value as a filling in selected cases of circumscribed abscess cavities in bone. Its use shortens the convales- cence and makes the dressings easy and painless. Simmons (Annals of Surg., Jan., 1911). Bismuth paste injection is an agree- able procedure, practically painless and free from risk, and of value in the treatment of chronic fistulae and abscess cavities. H. H. Schmid (Wiener klin. Woch., Nu. 7, 1911). The writer tried the effect of X-rays upon a case of chronic suppu- ration of very long duration, which had resisted other forms of treatment, including surgical operation. The suppuration was arrested, the part was healed, and the cure has lasted to the present time. Several other cases of a similar kind were then treated, and recovery obtained. Cum- berbatch (Lancet. May 16, 1914). In pyogenic infections the defen- sive tissue reaction awakened is purely local, general reactions being but slightly marked or absent. In order to be able to inject the germs in an absorbable form, the writer combines the Pasteur method of age- ing cultures with the modern pro- cedure of sterilization of cultures by heat. Much larger doses of the Del- bet vaccines — billions — of germs can thus he injected, without producing any "negative phase." On the other hand, severe reactions similar to Widal's "hemoclasic attacks" often result; though manifestations of tox- icity, these reactions are often a fa- vorable indication. In one caae an injection of 20 billions of germs in a case of very grave phlegmon of the hand was followed even by dysp- nea, asphyxial attacks, and cyanosis; but within 24 hours the local condi- tion improved and recovery very rap- idly followed. Experience has shown that the best dose of the vaccine is 4 c.c, containing about 13 billions of bacteria. The vaccine used is a stock preparation containing streptococci, staphylococci and pyocyaneus germs — the latter in large number, 8 bil- lions. The author does not believe in an essential specificity of vaccines; Wright has, himself, given up auto- genous vaccines, and has even ex- pressed a suspicion that vaccine pre- pared with a germ different from that causing an infection gives better clin- ical results. The pyocyaneus germ is chosen because it plays a useful role in relation to the streptococcus, hindering its development and attenu- ating its effects. In the last 6 years no case of carbuncle has been incised ABSCESS (WITHERSTINE). 205 in the writer's service. Recovery from boils, lymphangitis, and erysipelas is rapid under the vaccine treatment. Lymphaiigitic abscesses are given com- bined incision and vaccine treatment. Once sterihzation has been secured, the wound margins are brought to- gether with plaster strips to accelerate healing. Adenitis disappears in a few days under the treatment, or else softens very rapidly, so that after evacuation through an incision the parietes promptly come together again. This method is frequently in- dicated in abscesses of the wisdom teeth, in which the relative degree ot the glandular and the periosteal in- volvements is difficult to define. In subacute osteomyelitis, the procedure gave successful results in 3 out of 6 cases. Good results were likewise obtained in aeiite salpingitis. Recently definite improvement was noted in cases of gonococcic arthritis, althpugh specific serum had failed. Delbet (Presse med., Feb. 7, 1920). Antiferment Treatment. — This so- called "physiologic treatment" of abscess was introduced by. Miiller and Peiser. It is based on the antagonistic action the proteolytic ferment derived from leucocytes is supposed to meet from an antiferment in the blood-serum, especially in morbid effusions. This antiferment can be obtained from the patient's own blood-serum, after vene- section or from puncture fluids. The contents of the abscess being- aspir- ated, the antiferment is then injected into the cavity with the same needle, enough being introduced to fill it without distending it. The contents of the abscess are then again removed and the cavity is once more filled with fresh antiferment. This is repeated the next day if the area is still sensi- tive, the antiferment being left in. The writer has tried the injection of leucofermantin into abscesses — a treatment based upon the fact that a proteolytic ferment is found in the polymorphonuclear leucocytes. A fairly large needle was used for aspiration and injection, and, after evacuating the abscess, he injected and withdrew a small quantity of serum, so as to clean out the cavity as thoroughly as possible before making the final injection, which was allowed to remain; a moist aseptic dressing was then applied. If the aspiration had to be repeated, the needle was inserted through the old puncture, so as to save pain. The quantity of serum left in varied, ac- cording to the size of the abscess, from 2 to 15 c.c. The author feels convinced that the principle on which the method is based is sound, and that it opens up a new pathway in the physiological treatment of sup- purative inflammation. MacEwan (British Medical Journal, Jan. 22, 1910). Antiferment serum exerts a slight degree of curative action upon sup- puration, but must be brought into intimate contact with the whole of the suppurating surface. It is suited only for superficial, well-defined ab- scesses. Boit (Med. Klinik, Apr. 16, 1911). Surgical Measures. — Incision and drainage tersely indicate the surgical treatment of acute abscess. If sup- puration cannot be avoided, the ab- scess should be opened under rigid asepsis, as soon as an adequate quan- tity of pus has formed to constitute an abscess sufficient in size to be recognized by the surgeon as such (Senn), or as soon as the presence of pus has been determined by the ex- ploring needle or syringe. An early incision prevents excessive loss of tis- sue, less deformity and leaves smaller scar. If a local anesthetic is necessary, one of the following may be used : Twenty drops of a 1 to 5 per cent, solution of cocaine introduced sub- 206 ABSCESS (WITHERSTINE). cutaneously near the abscess; ether sprayed over the seat of the abscess until local numbness is experienced; chloride of methyl or chloride of ethyl vapor. The latter is especially efifica- cious; the parts turn white when ready, — generally in about two min- utes. Seltzer water spurted over the surface may be used to advantage when none of the other agents can be obtained. To open an ordinary abscess a single small incision suffices; but, if it is large, several small incisions should be made to render perfect evacuation of its contents possible by drainage. If the abscess is super- ficial, the skin alone should be cut, but if it is deep seated the skin and fascia should be incised and the grooved director, or the points of a pair of forceps, used to reach the pus, the opening being kept patent with forceps. The cavity is then thor- oughly emptied and syringed out with 1 : 10,000 corrosive sublimate solu- tion, or, better, witli normal salt solu- tion or boric acid solution, until the fluid comes out perfectly clear. Pres- sure with the fingers is to be avoided, but loose necrotic tissue should be re- moved if it can be done without injury to surrounding structures. The incision and its surroundings are then carefully washed with one of the solutions mentioned, and an aseptic drainage-tube inserted. The wound is dusted with iodoform or dermatol, and an antiseptic dressing is applied, exerting slight pressure with bandage. If the abscess is deep, the drainage- tube should be shortened daily; if it is superficial, the drainage-tube can be withdrawn the second or third day. Drainage by means of rubber drain- age-tubes of sufficient size is preferred to the use of gauze. Two tubes placed side by side facilitate irrigation when necessary. The necessity for radical treatment of any local suppurative process which persists in spite of conserva- tive treatment is emphasized by the writer. Such a suppuration is in numerous instances a grave menace to the body. Tubular drainage should be used only when a suppurating cavity is to be drained, when it is impossible to make a large opening, or when the drain cannot be safely inserted at the lowest point. The introduction of gauze into a suppurating cavity insufficiently opened is a blind and dangerous procedure. The best method of determining how and where gauze should be inserted is to introduce a gloved finger. D. Taddei (Riforma med., xxxvi, 447, 1920). When it is necessary to traverse the peritoneal or pleural cavity in order to reach a collection of pus, infection may be avoided by carefully packing ofif the cavity with gauze, so as to form a sort of well with the abscess at the bottom. The kind of dressing used after the abscess has been opened will depend upon the condition of the parts. If there be much infiltration of the tis- sues, swelling, and pain, a hot, moist antiseptic dressing is to be applied, as it favors absorption and is at the same time soothing to the patient. Any weak antiseptic solution (barring car- bolic acid for fear of gangrene) may be used, as boric acid, bichloride of mercury (not stronger than 1 to 20,- 000), or normal salt solution. The dressings (wet or dry) while suffi- ciently firm to favor collapse and adhesion of abscess walls should yet ABSCESS (WITHERSTINE). 207 be loose enough to permit of easy absorption and evaporation of dis- charges. COLD, OR TUBERCULOUS, ABSCESS.— Symptoms.— These ab- scesses frequently attain a large size, and last for months without their pres- ence being detected. Besides faiHng general health, the symptoms of the causative trouble are the only prom- inent ones. The spine, the hips, the genitourinary tract, and the lymphatic glands are the organs most prone to tuberculous disorders giving rise to cold abscesses. They sometimes ap- pear several months and even years after the beginning of the primary disease. The general symptoms of tuberculous abscesses do not closely resemble those of ordinary suppuration, but vary with the resisting pow'ers of the individual. There is nearly always a slight evening rise in temperature (hectic) follow'ed by a subnormal temperature in the morning. Loss of flesh and strength and the presence of anemia, more or less marked, are usual, although they may not occur unless mixed infection (tubercular and purulent) takes place. There is no leucocytosis. Amyloid (albumi- noid) degeneration may appear as a later phenomenon. The local symptoms are as a rule very slight, and are indicative of the effects of pressure upon organs or nerves rather than activity in the abscess itself. Large fluctuating abscesses may exist in various parts of the body, even about joints, wnthout serious dis- comfort to the patient. No pain is experienced as a rule; cold abscesses are not even tender to the touch. There is no redness until the abscess is about to break, the focus of the liquid mass being otherwise too deeply seated, the skin covering the abscess remaining white or normal in color unless the abscess be just be- neath the surface, which phenomenon has caused the name "white swelling" to be applied in tuberculosis of the knee. The above symptoms usually follow or are coincident with the sudden appearance of a swelling. Though generally soft, it may be hard, and suggest a tumor in the vicinity of the spinal column (Pott's disease), above or below Poupart's ligament, after burrowing along the psoas muscle (psoas abscess), on the inner aspect of the thigh, or in the lumbar region (lumbar abscess), etc. In the neck cold abscesses are usually due to dis- ease of the neighboring cervical lymphatic glands. The skin either remains normal or gradually becomes thinned and softened until an external opening is formed. Fluctuation, usually detected with ease, is sometimes hidden by a thick investing layer of lymph, which gives the mass a peculiar tension, suggest- ing a lipoma or some other hard growth. Aneurisms sometimes con- vey the sensation produced by a cold abscess : a fact to be borne in mind when operative procedures are under consideration. Pathology. — A cold abscess can al- ways be traced to a specific inflam- matory process, and almost invariably to one of a tubercular nature. Where the confluent masses in the center of a nodule begin to break down, there is formed a collection of material sur- rounded by tuberculous tissue. This material becomes infiltrated with leu- cocytes, and thus is produced a cavity containing fluid fatty material, frag- 208 ABSCESS (WITHERSTINE). ments of cells, and leucocytes, around which there is granulation tissue filled with tubercles. In this way a tuber- culous abscess is formed. It seems at times to be quite a matter of accident whether the abscess breaks into the joint or finds its way by a more cir- cuitous route into the surrounding connective tissue. As the tubercu- lous masses spread, caseation takes place at different points in the wall, and the masses are discharged into the cavity of the abscess; but the spread of the abscess is effected gen- erally l)y what is termed "burrowing of pus." This burrowing occurs in various directions, and large collec- tions of pus altogether out of propor- tion to the original lesion are formed, and are known as cold abscesses. What has been called a chronic ab- scess is very often no abscess at all. In tubercular processes the product of tissue proliferation undergoes co- agulation necrosis, and disintegrates into a granular mass, which, when mixed with a sufficient quantity of serum, forms an emulsion that micro- scopically resembles pus, but under the microscope shows none of the histological elements which are found in true pus. An abscess can only be called such if it contains pus. A true chronic abscess can originate in a tubercular, actinomycotic, or syph- ilitic lesion, when the granulation tissue is secondarily infected by the localization of pus-microbes, which convert the embr\^onal cells into pus- corpuscles. Differential Diagnosis. — The con- comitant disorder usually makes a diagnosis easy in a case of cold ab- scess ; but occasionally the swelling is the only indication of ill healtli, and it is important to determine, under such circumstances, the nature of the pus. The macroscopical appearances of "laudable" pus and of "sanious" pus are frequently so similar that a de visu diagnosis is not justified. Bac- teriological examination of the con- tents of such abscesses will show con- clusively whether the}' are true pus- containing abscesses or whether or not they are pseudo-abscesses. If cultivations are made of their con- tents, pus-microbes will grow upon proper nutrient media if it be a true abscess, while from the contents of a pseudo-abscess only the microbes of the primary infection can be cul- tivated. The information obtained by the discovery of the essential cause can be confirmed by inoculation experiments. Prognosis. — Tlie walls of cold ab- scesses are usually tense and tough, and are lined with cheesy tuberculous material. They d(j not tend to col- lapse, as is the case with acute absces- ses, and for that reason are healed with difficulty. When, however, the seat of tlie original trouble can be reached and successfully treated, the fluid in the parts of the abscess tract is absorbed, and the caseous matter undergoes calcification. This fortu- nate issue of the case is seldom met with, however, and the abscess usu- ally continues, the primary etiological factor acting as a drain for the dis- eased area. The prognosis, therefore, depends upon the result obtained in the treatment of the latter. Surgical Treatment. — Experience has shown that when such a cold, or tuberculous, abscess opens spontane- ously, or is incised in a careless way. profuse suppuration and hectic fever follow, Avith only too often a speedy fatal result from septic infection. ABSCESS (WITHERSTINE). 209 Unless the surroundings of the patient admit of carrying out the antiseptic treatment to its full and perfect ex- tent, a chronic abscess should not be evacuated by incision. It should be aspirated. Incision of a cold abscess dooms it to infection with all of the dire consequences from chronic sinuses through amyloid disease to death. Even retrophar^-ngeal ab- scesses should be drained only through aspiration. In very chronic cold abscesses cure is not infre- quently possible as a result of re- peated pioncture and complete aspira- tion with suction. E. A. Rich (X. W. Med., July, 1916). Our associate editor, Prof. Robert T. Morris, of New York, referring to tuber- culous glands of the neck (see also Ade- nitis, this Index), called attention two years ago to the fact that in the large number of cases treated by him in the New York Post-Graduate Hospital in re- cent years, he had only resorted to opera- tion those abscesses that were actually suppurating. All others were treated con- servativelj' to avoid general infection, in- cluding miliary tuberculosis. In a number of cases the use of the new high-pene- trating X-ray proved most effective. More recently he has added tuberculin to the other resources, and is convinced that when this method is applied in the right way and for a sufficient length of time it is one of our most important resources against tuberculosis of any kind. Evacuation of abscesses of tuber- culous nature by incision should never be done; aspiration and injec- tion of these abscesses is at the pres- ent time the preferable course to pur- sue. The injection fluid consists of: OHve oil Siiss (75 c.c). Ether . . .- 5i-^ (37 c.c). Creosote 5iss (6 c.c). Guaiacol gr. xv (1 Gm.). Iodoform 3iiss (10 Gm.). Of this mixture, ^ to 1 ounce (7^ to 30 c.c.) is injected, depending upon the age of the patient and the size of the abscess. The abscess is as- pirated and injected every 10 days 6 times. For fistulas and sinuses the following paste is used: Camphorated phenol, Camphorated naph- thol, of each .... 5iss (45 c.c). Guaiacol 5iiiss (105 c.c). Iodoform 5v (20 Gm.) . Creosote 5ij (8 c.c). Lanolin, Spermaceti, of each. 3xiij (50 Gm.). The sinuses are injected every seventh day and a large sized urethral glass syringe is used. The sinuses communicating are held closed until the paste is solidified. C. \V. Delany (Penna. Med. Jour., July, 1917). On general principles, necrosed or detached bone should be looked for in all cases. Strict antiseptic precautions are imperative to avoid mixed infection (bacilli of tuberculosis and pyogenic cocci). Preliminary precautions should be taken to meet violent hemorrhage due to vascular erosion. \\'hen there is local inflammation and spontaneous opening of the abscess is probable, there should be a free inci- sion, a thorough scraping of its walls with \'olkmann's curette to transform the suppurating surfaces into bleeding ones. The cavity is then cleansed with a 5 per cent, solution of carbolic acid, a long drain is applied, and the wound is stitched as far as the drain. An anti- septic dressing is then applied. (Volk- mann, Trelat, Pozzi.) After opening the abscess the cavity may be washed out with peroxide of hydrogen in 10 per cent, solution or packed with iodoform gauze. Removal of the limiting sac is then performed by decortication, the steps being: free incision, the sac detached with finger or spatula and removal, and the cavity closed immediately. (Lannelongue.) The removal of the limiting sac is facilitated by filling the wound with 1—14 210 ACETANILIDE (SAJOUS). paraffin ; tlie mass can then be removed as if it were a lipoma. (Cazin.) A psoas abscess should be opened in the loin and groin when possible. In the loin the incision should be made through the external and internal ob- lique, transversalis, and lumbar fascia, along the outer edge of the erector spine to the edge of the quadratus lumborum. The latter muscle and the transversalis fascia are divided on a level with the tij) of the second or third lumbar trans- verse process, avoiding the luni1)ar ar- teries. The sheath and the jisoas are tlien perforated with the finger or a trocar. A counteropening is then made below Poupart's ligament to form a tunnel, into which a large-size drainage- tul)c is inserted. This is replaced, later on, by a tube at each end to obtain oblit- eration, beginning from the center of the canal. If one incision is preferred the loin should be selected. Aspiration and Injections. — When no local inllammation indicates that the abscess is soon to open, the fluid may be withdrawn with a large aspirator; a 5 per cent, solution of carbolic acid is injected and then aspirated. This pro- cedure is renewed until the solution withdrawn is perfectly clear. A Lister bandage is then applied, insuring slight pressure. Five days later the treatment is renewed. About five sittings are re- quired. Injection fluids: Iodoform, 1 part; ether, 5 parts ; distilled water, 5 parts. Injection not to be renewed while iodo- form is being excreted in the urine. Less painful is a mixture of 1 part of iodoform to 10 of glycerin (Billroth) or of olive oil (Bruns). Intoxication may be prevented by sterilizing the iodoform and excipient (except ether) by heating at 212° F. separately. Boric acid, a 4 per cent, solution, may be used as above (Menard), or naph- thol and camphor, 1 part each. About thirty sittings are usually required. The lesion being a tuberculous one, the general system should be treated ac- cordingly. Nutritious food, including a free supply of milk and eggs, pure air, sunlight, and sea-air, if possible, are indicated, as well as tonics and alteratives (codliver oil and hypo- phosphites, iodine, iodides, arsenic, quinine, strychnine, etc.). C. Sumner Witherstine. Philadelphia. A. C. E. MIXTURE. See Chloro- form. ACETANILIDE.— Acetamlidum, formerly known under the name of aiitifcbritic, is obtained l)y boiling aniline with glacial acetic acid. It is the monacetyl derivative [CgHs.NH.- CH.rO] of aniline. PROPERTIES. — Acetanilide oc- curs as a white or colorless shining powder or as crystalline laminae. It is odorless, but has a slightly burning and bitter taste. DOSE. — The dose of acetanilide is 3 to 5 grains (0.2 to 0.325 Gm.) in adults ; the tendency, however, is to employ smaller quantities. In chil- dren, according to Griffith, the coal- tar products of this class are well borne; ^ to J/2 grain (0.016 to 0.033 Gm.) may be given at 6 months, increasing the dose by ^ grain w^ith each year, until the adult dose is reached. The action of acetanilide should be closely watched in weak subjects and in hysterical women. Out of 274 observers who stated that they used acetanilide, 17, or 6.2 per cent., employed less than 2 grains as a mini- mum dose for adults: 113, or 41.2 per cent., employed 2.5 grains or less as a ACETANILIDE (SAJOUS). 211 minimum dose, and 155, or 56.5 per made combinations. The foundation of cent., employed from 3 to 5 grains as most of the coal-tar product combina- a minimum dose. Two hundred and tions is acetanilide, which has been corn- forty, or a little over 87.5 per cent., bined with bicarbonate of soda, caffeine, never exceeded a dose of 5 grains, and carbonate of ammonia, etc. The com- 34, or not quite 12.5 per cent., employed bination may be chemical or mechanical, doses exceeding 5 grains. it matters little which, as it is practically An examination of a number of pre- broken up in the body into acetanilide scriptions for adults on file in vari- radicals and other constituents. L. Fau- ous pharmacies in Washington, D. C, geres Bishop (Med. News, June 10, brought into court as evidence, showed 1899). the average dose of acetanilide pre- Various combinations of acetanilide scribed was 2.43 grains. Kebler, Mor- ^jt^ other drugs (adjuvants and corri- gan and Rupp (U. S. Dept. of Agricul., gents) may be made to meet the exi- Burcau of Chemistry, Bulletin No. 126, gencies of practice, some of which are July 3, 1909). as follows :— MODES OF ADMINISTRA- ^ ^,,,a,„7.rfi gr. xij (0.800). TION. — Acetanilide is insoluble in Caffeina: citrata gr. nj (0.200). , ■ r 1 ii 1 ui • 4. / 1 Campliora: mono- glycenn, slightly soluble m water (1 ^^^„^ „^^.-^ (0.400). grain in 3 fluidrams of cold, and 1 Misce et fiant capsulse no. vj. grain in 18 minims of hot, water), Note.— The caffeine and camphor are but completely so in alcohol (1 "sed as corrigents to the acetanilide. grain in 2>4 minims"), and readily in ^ AcetanUidi gr. xv (1.000). , ^.. ..,„.. . T • Sodii bicarbonatis .. gr. x (0.650). ether (1 gram m 18 mmims). It is Ammonii carbonatis. gr. xv (1.000). readily suspended in syrupy mixtures Misce et fiant capsulae (not pulveres) and can be given with most drugs "°- ^• thus administered. Acetanilide is . NoxE.-The sodium bicarbonate aids m the assmulation of the acetamhde, also dispensed by druggists in the while the ammonium carbonate acts as form of tablets, which are quite taste- ^ corngent. less when taken w^ith a mouthful ^AcetanUidi . . gr. xx (1.300). Soda bicarbonatis. gr. xv (1.000). of Avater. It may be given in the Caffeince gr. vj (0.400). form of powders or in dilute alcoholic ^^jdi citrici gr. x (0.650). , , • Misce et fiant capsulae (not pulveres) solutions. no X f \ f There was also formerly official the NoxE.-The caffeine and citric acid in compound acetanilide powder (pid- the above should be mixed and slightly vis acetanilidi compositlis), contain- moistened; this allows the formation of ing acetanilide, 7 parts; caffeine, 1 a fresh preparation of citrated caffeine; , J J- 1 • u .1- /i • it should then be dried and mixed with part, and sodium bicarbonate (to in- , , . ,. ^ 1 ,. r 1 • t"^ other mgredients. crease the solubilitv of the acetani- ,.j . o 0. .Li j' r u- u • c R Acetanilidi gr. xx (1.300). hde), 2 parts, the dose of which is 5 ^^^j- bicarbonatis. gr. xx (1.300). to 10 grains (0.3 to 0.6 Gm.). Sodii salicylatis . 3iss (6.000). ixruM i -i-j • t 1 ui ^„A Misce et fiant chartulse no. x. While acetanilide is not soluble and is readily suspended in syrupy mixtures, Note.— The sodium salicylate is used it can be combined with ammonia in as a synergist to the acetanilide. any of its forms, salicylic acid, nux IJ Acetanilidi gr. xx (1.300). vomica, digitalis, codeine, creosote, po- Potassii bromidi . gr. xxx (2.000). tassium bromide, etc. A prescription Sacchari lactis ... gr. xv (1.000). can therefore be elaborated that can Misce et fiant chartute no. vj. be much more accurately adapted to the Note. — The potassium b'-omide is case in hand than any of the ready- used as a synergist to the acetanilide. 212 ACETANILIDE (SAJOUS). I^ Acetaiiilidi gr. xxv (1.600). Poiassii bromidi . gr. xv (1.000). Caffeince citratce . gr. v (0.325). Misce et fiant capsulae no. x. U AcetanUidi gr. xxv (1.600). Sodii bicarbonatis . gr. x (0.650). Caffeine citratce . gr. vj (0.400). Camphorcc mono- bromatcc gr. vj (0.400). Misce et fiant capsulcc no. x. IJ AcetanUidi gr. x (0.650). Sodii bromidi gr. l (3.250). Extracti hyoscy- aiiii gr. V Caffeince citratce . gr. v Morphince sulphatis. gr. % Misce ct fiant tabclke (or capsulse) no. X. Note. — The sodium bromide, extract of hyoscyamus, and morphine sulphate all act as synergists to the acetanilide, while the caffeine corrects their action. (0.325). (0.325). (0.013). Vi.) u (0.325). (0.163). (0.0065). (0.013). T^ AcetanUidi gr. xx (1.300). Quinincc suiphatis gr. xx (1.300). Extracti hyoscy- ami gr. v Extracti cannabis hid gr. iiss Arseni trioxidi . . gr. Strychnince sul- p'hatis gr. Misce et fiant tabcllie (or capsulae) no. .X. ]S[oTE. — The strychnine sulphate is used instead of the caffeine as a cor- rigent. R AcetanUidi 5j (4.000). Zinci oxidi 5j (4.000). Amyli q. s. ad 3j (32.000). Misce et fiat pulvis. Sig. : Use as a dusting powder. Ji. AcetanUidi 3j (4.000). Adipis lance 3ij (8.000). Petrolati ..q. s. ad 5j (32.000). Misce et fiat unguentum. R Antipyrince 3j (4.000). Caffeince citratce .. gr. xx (1.300). AqucE destillatce . iSiv (120.000). Misce et fiat solutio. Sig.: Teaspoonful as required. Note. — In the above prescription anti- pyrin is used, as it is very soluble, while acetanilide is almost insoluble. \V. K. Foreman and J. H. Gertler (Jour. In- diana State Med. Assoc, June 15, 1909). It has been supposed that the addi- tion of caffeine to acetanihde decreased its toxicity, and, therefore, the likeli- hood of untoward effects. Hale has shown experimentally, however, that such was not the case, and, indeed, that it greatly increased it. Sodium bicar- bonate, on the other hand, tends to les- sen the toxic effects of acetanilide upon the lieart. By experiments on the hearts of warm- and cold- blooded animals the writer found caffeine of little or no benefit in acetanilide poisoning in so far as the cardiac energy and the blood- pressure were concerned, and that it apparently exerts a harmful eft'ect in some cases. But there appeared, espe- cially in the dog, to be a well-established antagonism on the heart rate which, however, would probably be insufficient to be of any value in cases of poisoning in man. Feeding experiments demon- strated the absence of antagonism be- tween acetanilide and caffeine, in all cases the addition of the latter drug causing death more quickly or with a smaller dose. This, in connection with the imperfect antagonism to the heart action, makes the use of caffeine in acetanilide mixtures especially question- able. Sodium bicarbonate, in contrast, lessens the to.xicity of acetanilide, both in its action on the heart and on the intact animal, increasing the duration of life or making the use of a larger dose of acetanilide necessary to cause death. Hale (Jour, of Pharmacol, and Exper. Therap., Aug., 1909). INCOMPATIBLES.— Acetanilide forms insoluble compounds with the bromides and iodides in aqueous solu- tion, and a soft mass on trituration with chloral, carbolic acid, thymol, or resorcinol. According to Blackwood, unexpected and often alarming effects are observed when calomel is given with any coal-tar product. CONTRAINDICATIONS. — Ace- tanilide should not be used when the heart is fatty, weak, or enlarged ; in blood disorders such as pernicious ACETANILIDE (SAJOUS). 213 anaemia characterized by cell destruc- tion ; in phthisis or other exhausting diseases, and in pregnant or nursing women. PHYSIOLOGICAL ACTION.— As Antipyretic. — In the normal sub- ject, the temperature, according to Nothnagel and Rossbach and most authorities, is lowered only when toxic doses are given. Not so, how- ever, when fever is present. Here a small dose suffices to produce a marked fall. Dujardin-Beaumetz, for example, witnessed a decline of 3° C. (5.4° F.) and cyanosis in a case of t3'phoid fever in which 7^^ grains (0.5 Gm.) had been administered. Manquat states that 1 3/2 to 3 grains (0.1 to 0.2 Gm.) suffice to influence the temperature, acetanilide, accord- ing to Krieger, Calm and Hepp, being far more active in this particular than antipyrine. Sweating and chills are occasionally observed. The investigations of Hare and Evans suggested that the fall of tem- perature produced in febrile cases was due to a decreased heat-production and increased heat-dissipation. But Wood, having found that the rectal temperature not only did not fall as did that of the surface, but that it rose, concludes that the experiments of Hare and Evans "cannot be used to explain how antifebrin reduces the temperature." Moreover, most Euro- pean investigators, Lepine, Podanow- sky and others, hold that acetanilide acts by depressing the heat-center. According to Cushny, it affects the nervous heat-regulating mechanism in such a manner as to lower the level at which the body-temperature is maintained, the loss of heat necessary to produce the fall in temperature be- ing accomplished by dilatation of the cutaneous vessels. The manner in which acetanilide acts as an anti- pyretic is stated by Butler to be far from understood. Action as Analgesic. — According to the prevailing view, acetanilide acts directly as a sedative upon the nerv- ous system, especially upon the sen- sory portion of the spinal cord; with toxic doses the effect may extend to total loss of reflex action and sensory and motor paralysis, the muscles be- ing influenced only directly. Wood holds that, "directly or indirectly, ace- tanilide affects the cerebral function," though at a certain stage of its toxic action consciousness may be uninflu- enced while the rest of the nervous system is clearly affected. Bokai ascribes the effects of acetanilide to paralysis of the motor nerve-endings in the muscles, sufficiently prolonged exposure of the latter to the poison also annulling their ability to con- tract. Cushny, referring to this and other coal-tar products, states that "by many the}' are supposed to have a sedative or depressant effect on the nervous system." The analgesic action of acetanilide is generallv as- cribed to this supposed sedative eft"ect, though all agree that applied locally to the tissues it acts as a stimu- lant or mild irritant. Its toxic eft'ects, however, should not be overlooked. Action on the Blood. — The cyanosis produced by excessive doses of ace- tanilide is ascribed by Lepine. He- nocque and others to transformation of the hemoglobin into methemoglo- bin, and by Vierordt, Halliday and others to the reduced haemoglobin as it occurs in venous blood. Some con- tend that the red corpuscles are dis- organized, while others hold that they remain intact. 214 ACETANILIDE (SAJOUS). Acetanilide, antipyrin, and acetphe- netidin lower the total amount of oxygen in the circulating arterial blood. The diminution is slight with antipyrin, which, in fact, in large and medium-sized doses causes at first an increase. With the other two agents the decrease is both pronounced and constant. The variations in the amount of carbon dioxide in the blood are not parallel with those in the oxygen. The respiratory func- tional capacity of the blood and the respiratory interchanges are dimin- ished. Piccinini (Arch. Inter, de Pharm. et de Therap., vol. xxii, Nos. 1 and 2, Cyclo. Suppl., 1918). Action on the Circulation. — Injec- tions of acetanilide in animals have been found to cause at first a slight increase in the number and force of the heart-beats, with corresponding rise of blood-pressure. Later, and also from the first with larger doses, circulatory depression is observed. In febrile patients the lowering of temperature produced by the drug is often accompanied by reduction in the frequency and size of the pulse. Large doses are said to depress the heart directly. [These phenomena are the normal results of the exciting action of the drug upon the sympathetic center and the resulting con- striction of the arterioles. Those of the heart admitting less blood into its muscular walls, the force of its contractions and their number are reduced. The heart's action may be arrested by the same process. C. E. DE M. S.] UNTOWARD EFFECTS AND ACUTE POISONING.— The symp- toms of poisoning include primarily the cyanosis, which begins at the lips and then extends, gradually becoming more intense, over the face and the rest of the body, and is accopipanied by profuse sweating and prostration. In some cases there is ashen lividity and the temperature falls rapidly to 95° F. or lower. The pupils are dilated and fixed. The respiration is slow and shallow, and the pulse be- comes steadily weaker and then irreg- ular and fluttering. Somnolence, un- consciousness and coma, and cardiac arrest follow. In some instances sudden heart-failure occurs soon after the onset of the symptoms, the organ being arrested in diastole. Erythem- atous or urticarial skin eruptions and disorders of hearing are occasion- ally observed. An instructive case was published by Ballou some years ago. The patient was a man, aged 45, suffering from a form of intermittent fever. He complained of al- most unbearable headache; pulse. 120; respirations, 23; temperature, 104.8° F. Ten grains of acetanilide were given, and about 20 minutes later the patient said his headache was relieved, and that he felt easier. About 45 minutes after the drug was administered all sweating ceased, and a peculiar sensation of warmth under the skin was complained of. To this, in 12 or 15 minutes, was added intense itching, while in 3 or 4 minutes the whole body presented a general erythematous condi- tion. The entire surface was of a brighter red than that of a typical case of scarlet fever, and, like the scarlatina rash, it dis- appeared on pressure, to return as soon as pressure was removed. Xo part of the body was exempt from this rash, the con- junctivae, palms of the hands and soles of the feet being as red as any part of the body. The temperature of the surface seemed elevated, but the thermometer in the mouth showed that it was gradually falling. The body appeared as if every superficial capillary was dilated. With the appearance of the rash the itching became more intense, the patient assuming all positions possible while scratching. Within the external ear the itching was especially intense, but there was no disturbance of hearing. The rash lasted for 6 hours, without any apparent change, and then disappeared rapidly from all parts of the body simultaneously, and as the rash faded the itching subsided. ACETANILIDE (SAJOUS). 215 About this time a slight cardiac irregular- Out of 288 practitioners questioned, ity became evident, and this lasted for 4 219, or 76 per cent., stated that they days. The only drug taken before the had observed instances of poisoning acetanilide was calomel (about 5 grains). following the use of acetanilide. These The 2 unusual symptoms, intense itch- 219 observers report 614 cases of poison- ing and general erythema, were due to ex- ing, including 17 deaths, i.e., 2.7 per cent, cessive dilatation of the arterioles after The character of these cases and the the true toxic effects had passed off, the doses used were as follows: — violent excitation to which the poison had ^ . , , . , , , . , . Pneumonia (child) .. .One-half grain every 2 subjected the sympathetic center havmg hours until 2 grain-s temporarily exhausted it. Editors. Capiiian- bronchitis ^'^'^ '^''^°' According to the writer, study of ^''^'^^> ^'^feplatld.*'"^''"^''"'' the cases recorded in the literature CapiUary bronchitis , , , , (child) Small doses frequently and personal cases proves that the repeated. ingestion over a considerable period T^-phoid Five grains ever>- 4 hours .- .• r 1 -I- 1 1 i J 1 Headache About 20 grains. ot time of acetanilide or related coal- „ ^ ,_ ^„, . si«i'"^- . . , Headache Thirty grains (?). tar products is productive Ot a detl- Headache "Orangeine" taken freely nite symptom-complex which is Headache Thirteen or fourteen 5-grain highly suggestive, if not absolutely „ . . ^ '^°'^' '° ^- ^°''''- •^ ■> '=>i=> ' ■' Headache Bromoseltzer. diagnostic, of poisoning by this Neuralgia Dose not ^iven. group. The subjective SJ'mptoms Xeuralgria of heart... Five 5-grain doses in 5 are: great general weakness, nervous .^ „ °"'^^' .. . , . . . . . Burn Boroacetanilide applied excitability, insomnia, loss ot appe- freely. tite, digestive disturbances, palpita- Burn 'infant) Acetanilide applied freely to umbilical cord. tion, dyspnea, numbness and weak- Headache Excessivedosesof 'bromo- ness of the extremities, pain in the seltzer." r ,1 1- J 1 A T>-phoid f child) Five grains. region of the liver and spleen, and „ ^, ■., t t,-,^, t^ . . "= ^ ' Typhoid (child) Dose not given. faint attacks. The chief objective Malaria (child) One and one-half grains. S3'mptoin is cvanosis, which is often t- ui -m in /rr r- t^ \ . ' ,, a . . . Kebler, Morgan and Rupp (L. S. Dept. extreme, but usually fluctuating in in- r \ • i r> r rA • n , . , , , , , of Agricul., Bureau of Chemistrv, Bul- tensity, accompanied by marked pal- , ,. n-y ^^ ^ , , -.ru^^ :\ / , ■ , letin No. 126, July 3, 1909). lor of the mucous surfaces and with- out clubbing of the lingers. Experiments conducted by the The blood-changes are quite char- ''""^^ ^° ascertain whether acetani- acteristic, and due to the destructive ^'^^ appeared in the milk of a nurs- action of a hemolytic poison circulat- '"^ mother, and, if so, whether in ing in the blood-stream, which pro- sufficient quantity to cause the death duces a secondary anemia variable ^^ ^" '"^=^"t- ^hey showed that in degree. The erythrocytes are di- acetanilide derivatives are at times minished in number; they often pre- eliminated, but that more frequently sent nucleated forms, show granular ^^^''^ '^ "° ^'"^^^ °^' them in the stippling, stain poorlv, and are vari- maternal milk or the infant's urine, able in size and form There is usu- ^he quantity found in each case was ally a moderate leucocytosis of the ^° minute that it could only be de- poiymorphonuclear variety, and there ^^"^^^^ ^^ holding the specimen is often a relative increase of the against a white background. The lymphocytes. The appearance of the ^'"^^ ^^ ^^^^ ^^^t appearance of the blood as it stands upon the finger- reaction after the administration of tip or the ear is very suggestive; it ^ d°se of 4 grains varied from 7 to is either of a bluish-black color or 1^ hours. Stevenson (Mich. State chocolate in appearance. The col- ^ed. Soc. Jour., Apr., 1914). oration of the plasm.a renders the t^, ^ • •, p i ,- ., , , ,. ., 1 he srreat maiontv of such cases estimation ot the hemoglobin quite ^ ^ difficult. Gordinier (Monthly Cyclo. ^re due to intoxication by proprietary and Med. Bull., Mar., 1912). headache powders sold under a vari- 216 ACETANILIDE (SAJOUS). ety of fancy names. Proprietary prep- arations containing acetanilide were re- ported to have been used in 77 , or 12.5 per cent., of the 614 cases of poisoning mentioned above by Kebler, Morgan, and Rupp. It is well known that certain individuals show an idiosyncrasy to the drug, and in some instances very small doses will suffice to cause death. Many instances of "headache powder" victims have been published. Philip Brown, for instance, observed a case of fatal poisoninjT from this cause. The pa- tient, a man of 2>1 , had taken si.\ "head- ache powders" each containing 10 grains. He became delirious, complained of ab- dominal pain, vomited, and was slightlj' jaundiced. His temperature rose to 100.2° F. (37.9° C), the lips and nails became in- tensely cyanotic, respirations shallow and frequent. The urine, of which 10 ounces were passed on admission, was nearly black and strongly alkaline. Anuria oc- curred, and 6 days later the man died. There was alternate constipation and diarrhea, and 48 hours before death the feces constantly showed blood-pigment, blood-clots, and corpuscles. Another case of acetanilide poisoning with fatal results following the ingestion of "bromoseltzer" taken to relieve a head- ache, was published by Hemenway. The heart, already weakened from repeated doses of the drug, was unable to stand a slight overdose and the victim died in a few hours. In a case of acetanilide poisoning, observed by Summers, in a woman, aged 26 years, who had taken 8 grains, there occurred collapse with strong convulsive movements, partial loss of consciousness, and great retching. Whisky, strychnine nitrate, and — for two hours — artificial respiration in- duced recovery. In another instance observed by Earps the patient had taken four headache powders. These had been taken each hour between nine and noon. The surface of the body pre- sented an ashen-gray appearance, the mucous membranes having a much darker hue. The temperature was 96 degrees; pulse, 60, and respiration. 10. Digitalis, strychnine, and alcohol baths with friction were employed, with dry heat to the surface. When the i)atient was able to swallow, a cf>ml)ination of aromatic spirit of am- monia, brandy, and capsicum was given. Twenty-four hours later the temperature was slightly subnormal, the dusky appearance of the face dis- appeared to a large extent, but the symptoms of cyanosis did not wholly vanish until the second day. The powders contained 3 grains of acet- anilide. 2 grains of bicarbonate of sodium, and 1 grain of caffeine ; hence the total dose was 12 grains of acetanilide. The doses capable of producing toxic efifects are sometimes very small, but it is ])robable that some of the drugs recommended in textbooks for the treatment of poisoning by coal-tar products, strychnine and belladonna, for example, do more harm than goo'stals of orthonitrobenzaldehvde in boiling water; on cooling down the aldehyde forms a wdiite, milky cloud; the fluid ACETONURIA (LEVISON AXD ERLANDSEN). 235 which is to be tested is now added and the mixture rendered alkaline with a solution of sodium hydrate. When acetone is present a 3'ellow color will appear, which changes to green and, after ten minutes, to indigo ; it also forms an indigo-blue precipitate. Very small quantities of acetone may be detected by shaking the mixture with a few drops of chloroform. When left quiet for some time the chloro- form takes a blue color and sinks to the bottom of the test-tube. According to Penzoldt, acetone is revealed bv this test in a solution of 1 to 2000. According to von Jaksch, the smallest quantity of acetone revealed by it is 1.6 mg. Aldehyde acetophe- none and other substances form in- digo in the same way as acetone, but the color is not so marked. Malerba's Test. — Malerba found that a Vj per cent, solution of parami- domethylaniline with acetone gives a reddish color, changing into violet and blue-red. Riegler describes the following test : 15 cm. of urine are acidulated with 5 to 10 drops of concentrated sul- phuric acid. When 2 to 3 c.c. of an aqueous solution of iodic acid are added, an intense pink color will ap- pear, which is not taken up by chloro- form. The test has been found to be specific and active where Legal's test fails. Frommer renders the urine strongly alkaline with potassium hydrate and adds several drops of a 10 per cent, solution of salicylic aldehyde, and heats to 70° C. A purple ring appears if the reaction is positive. Miscellaneous Tests. — With bisul- phite of soda, acetone, as well as the aldehydes, combines to a crystallic compound in thin flakes resembling those of cholesterin, even by micro- scopic examination (Limpricht). Acetone in an alkaline solution com- bines with iodine to form iodoform. Freshly precipitated oxide of mer- cury is dissolved by acetone. Indigo is formed when acetone is combined with orthonitrobenzaldehyde in an alkaline solution. (Baeyer and Drew- sen.) From what has just been stated it will become apparent that not one of the tests is specific for acetone alone. To be quite sure that acetone is contained in the distillate, it is nec- essary to try successively by all the tests, and only when all tests give positive result is the presence of acetone proved. A. E. Taylor is of the opinion that only the tests described by Stock and Deniges are really good and reliable and should replace the tests with Lugol's solution, mercuric oxide and sodium nitroprusside. The only two really good tests for acetone in the urine are that of Stock, described in 1899, and that of Deniges, described in 1898. These are certain in their results and easy of execution, and should replace the fallacious tests with Lugol's solution, mercuric oxide and sodium nitroprusside. The two tests agree ; the writer has never had the Stock test present without the Deniges test being also positive. The Stock test is less sensitive than the other, but this is considered an advantage for prac- tical purposes. The author has often found acetone present by these tests without obtaining the reaction for diacetic acid, for which he also gives the method ; but he has never found diacetic acid present without acetone. A. E. Taylor (Jour. Amer. Med. Assoc, Mar. 17, 1909). he quantitative estimation of the acetone bodies is often most impor- tant as an indicator of the degree of 236 ACETONURIA (LEVISON AND ERLANDSEX). derangement of metabolism and aci- dosis that may be present. Von Jaksch has tried to employ the nitrocyanide test for a quantitative estimation of the acetone, and the iodoform test has been recommended by ]\Iessinger and Iluppert for the same purpose. The quantity of iodine used to form iodoform with the ace- tone is measured (titrated), and the quantity of the acetone present in the solution calculated by it also; but, although Engel and Devoto are of the opinion that it is possible to make pretty accurate estimations in this way, methods for quantitative estima- tion of the actone are not to be relied upon, as it is impossible to avoid errors caused by the presence of sub- stances which arc influenced by the tests in the same way as the acetone. Diacetic acid (C4TT(;03=CH3— CO —CHo— COOII) may be revealed in llie urine by the aid of a solution of perchloride of iron (Gerhardt's test), which, with diacetic acid, produces a dark wine-red color. The test is made by adding a solution of per- chloride of iron as long as a precipi- tate of phosphates of iron is formed. The mixture is then filtered and some drops of perchloride are added to the filtrate. When diacetic acid is present, the filtrate takes a deep-red color, which vanishes in twenty-four hours, and more rapidly after addition of strong acids. Von Jaksch has, by a colorimetric method based on this test, tried to make an approximate estima- tion of the quantity of diacetic acid contained in the urine, but newly passed urine can alone be used for the search of diacetic acid, as this acid, after some time — twenty-four to forty- eight hours — will disappear from the urine. Diacetic acid can be isolated from the urine by adding a few drops of sulphuric acid and shaking the mixture with ether. When diacetic acid is present, it is dissolved in the etlier and can be detected by the per- chloride of iron test. Beta-oxybutyric acid (C4IISO3) is also found sometimes in the urine of fever patients, as well as in diabetes, with acetone and diacetic acid. This may also be the case in the dyspepsia of alcoholism and in carcinoma of the stomach, scarlatina, measles and scor- butus. When beta-oxybutyric acid is cautiously oxidated, acetone is found. For general practice the exact quan- titative determination of the acetone bodies is rather complicated. To overcome this difficulty, Stuart Hart (1908) devised a procedure based on the delicacy of the well-known test- tube reactions in urine. The urine is first tested for Gerhardt's reaction. If positive, we know the acetone bodies to be present in excess of 0.2 Gm. per liter. If the reaction is very strong, the test solution is diluted with dis- tilled water until the color approxi- mates that of the standard ferric chloride solution, and tin's dilution, when compared in one of the author's tables, gives the amount in Gm. per liter. If Gerhardt's reaction proves nega- tive, Arnold's, Legal's and Lieben's tests are tried in the order named. A positive Arnold reaction indicates Ca 0.1 Gm. per liter; positive Legal reac- tion Ca 0.03 Gm. per liter. If only Lieben's test is positive, the amount of acetone is within the normal limits. (See Acidosis, this volume.) F. Levison A. Erlaxdsex, Copenhagen. ACETOZONE. ACETPHENETIDIN (SAJOUS). 237 ACETOZONE, a germicide and de- odorant (accepted by the A. M. A. Coun- cil) formerly known as benzozone, is a mixture of acetylbenzoyl peroxide and an inert absorbent powder. It was introduced by Freer and Novy, of the University of Michigan. Its properties resemble those of hydrogen peroxide, though, according to its discoverers, it is over one hundred times more active as a germicide. Acetozone, in its original form, occurs as white shining crystals, but is marketed in the form of a powder. The latter should be kept perfectly dry, but it should not be exposed to heat, which decomposes and volatilizes it. It is also rapidly decom- posed by organic substances and should not be administered after a meal. Modes of Administration. — Acetozone is usually employed in the following manner: '"Add the powder to warm water in the proportion of 15 grains to the quart; shake vigorously for five minutes, and allow to stand for about two hours. Decant off the liquid as required. If the patient objects to the taste, a little extract of orange or lemon, or orange or lemon juice, ginger ale, carbonated water, or fruit syrup may be added to each dose as taken." It may also be given in capsules, but followed at once by a copious draught of water. It is soluble in water to the extent of 1: 1000 to 10,000: in its crystalline form in oils to the extent of about 3 per cent, and slightly soluble in alcohol, ether, and chloroform, but all these solvents grad- ually decompose it. This does not apply to neutral petroleum oils, however, and an "acetocone inhalant" is available which contains 1 part of acetozone, Yz part of chloretone, and 98.5 parts of refined liquid petroleum. It may be given in an ointment, using solid or liquid petrolatum as excip- ient, beginning with y^ per cent, strength. An aqueous solution may be used as spray and as a deodorizer and antiseptic for stools, sputum, etc. Therapeutics. — .A.cetozone is used for its marked oxidizing and germicidal action mainly for the treatment of diseased mucous membranes. It has been credited with a favorable action in typhoid fever, the main effect being decrease of the fetor of the stools, subsidence of the tympanites and diarrhea, and prevention of hyper- pyrexia. Good results have been obtained in Asiatic cholera. In ophthalmology, a solution of 1 grain to 2 ounces of water, instilling 1 drop or 2 every hour, has been found useful in corneal infections. In laryngology, tonsillitis and atrophic rhi- nitis have seemed to be beneficially in- fluenced. This applies also to infected wounds, gonorrhea, and chancroid. It has been found an excellent deodorant in gan- grene and malignant small-pox. Acetozone is a very efficient bac- tericide and antiseptic for use in the treatment of war wounds. It may be used in strengths of from 5 to 10 grains (0.3 to 0.6 Gm.) to the pint (500 c.c.) for wet dressings and irri- gations and to saturate gauze. It can also be used in the stronger solu- tions by Carrel's method. In very septic cases the strengths may be raised to 20 or even 60 grains (1.3 to 4.0 Gm.) to the pint (500 c.c). The solution keeps fairly well, but should be made fresh every week. Bacterio- logical tests showed that it was markedly germicidal toward Staphy- lococcus pyogenes as well as the anaerobic Bacillus mycoides, which is a spore bearer. Its germicidal power is considerably reduced, however, in the presence of serum, broth, or pus, but it still remains fairly efficient. C. Gore-Gillon and R. T. Hewlett (Brit. Med. Jour., Aug. 18, 1917). S. ACETPARAMIDOSALOL. See Salophex. ACETPHENETIDIN.— {acetphcnctidinnm; para-acetpheneti- din), commonly known under the pro- prietary name of phenacctin, is a coal- tar product, obtained by treating para- phenetidin with glacial acetic acid. It is an acetyl derivative [C6H4. OC2H5. NHCH3CO] of para-amidophenol. PROPERTIES.— Acetphenetidin OC-- curs in the form of a white, odorless, and practically tasteless powder, com- posed of small, needle-like or scaly crys- tals. 238 ACETi'ilENETIDIN (SAJOUS). DOSE.— Five to 10 grains (0.32 to R Acett^hcnctidim gr.xy (li) Gm.). ^ ^^ , . , ,, 1 c • /nnr- Caftemcc citratcc gr. viij (0.5 Gm.). 0.65 gram) in adults ; 1 to 5 grams (O.OOd ^-^^,-j jjromidi 5j (4.0 Gm.). to 0.32 gram), according to age, in chil- Elixiris glycyrrhiza; . Sj (30.0c.c.). dren. The maximum amount to be M. Sig.: Two teaspoonfuls, repeated if given in twenty-four hours, according to necessary. Shake well. Pouchet, is 30 to 45 grains (2.0 to 3.0 Where nausea and vomiting accom- grams), which should be distributed pany headache, oral administration be- during the day in several doses, each not ing, therefore, un.suitable, acetpheneti- exceeding 7^. grains (0.5 gram). The din may be administered by the rectum tendency is toward a marked decrease in 1 or 2 drams of water (Brunton). of this amount. Acetphenetidin is sometimes used lo- Out of 297 observers using acet- cally in powder form or in an ointment phenetidin, 10, or 2,Z per cent., em- or alcoliohc ])reparation. ployed less than 2 grains as a minimum INCOMPATIBILITIES. Acet- dose for adults; 90, or 30.3 per cent., ..... ... . ' / .. , , oc 1 o o ,^;^; i)henetidm is inconii)atiblc with iodine, employed 2.5 grams or less as a mmi- ' ' mum dose; 188, or 63.3 per cent., em- "itric acid, and o.xidizing agents gener- ployed from 3 to 5 grains as a minimum ally ; also with chloral hydrate, phenol, dose; 89, or 29.9 per cent., used doses .^^^^^\ salicyhc acid. exceeding 5 grains, while 2()8, or 70 CONTRAINDICATIONS.— These per cent., never exceeded a dose of 5 ■j^g are the same as those of acetamlide An examination of a number of {q-V.), though the dangers from its use prescriptions for adults on file in vari- are less marked than with the latter ous pharmacies in Washington, D. C, ^\^y^^ jj jg advisable not to employ it showed that the average dose of acet- j^^ ^^^^^ ^^ ,^^^^^ ^^.^^^^^^ pulmonary phenetidin prescribed was iyl grains. , , • • • Kcbkr, Morgan, anC Rupp (U. S. Dept. tuberculosis, grave anemia, or in per- of Agricul., Bureau of Chemistry, Bull, sons markedly enfeebled from any No. 126. July 3, 1909). other cause. MODES OF ADMINISTRA- PHYSIOLOGICAL ACTION.— TION. — Acetphenetidin is almost in- As Antipyretic. — Acetphenetidin is the soluble in cold water (1 grain in 2 safest and most frequently employed ounces), more freely soluble in boiling of antipyretic remedies. In common water (1 grain in 1 dram), and read- with acetanilid, it has little or no influ- ily so in alcohol (1 grain in 12 minims) ; ence on the temperature of normal indi- it will also dissolve in glycerin and lac- viduals in therapeutic doses, but causes tic acid. a fall in febrile cases. According to Being almost tasteless, it is easily Crombie and Hirschf elder, the greatest taken in powder form ; it can also be reduction is not produced until three or given in capsules, cachets, or tablets, four hours after administration. The When combined with other remedies in average decline may be put down as liquid preparations it is best kept in 3.6° F. (2° C. ;Manquat). The reduc- solution by dilute alcohol. Thus a mix- tion may last six to eight hours, and is ture of acetphenetidin, sodium bromide, free of unpleasant effects, excepting a and caffeine in the elixir of licorice is mild sweat (Pesce). Cerna and Carter frequently prescribed for the relief of found that acetphenetidin produced a headache. A good formula is the very slight fall of temperature during following: — the first and second hours after inges- ACETPHENETIDIX (SAJOUS). 239 tiori, and that the effect reaches its or, possibly, asphyxial origin (Cushny). lieight in the third hour. They beHeve H. C. Wood, Jr., and H. B. Wood that the fall of temperature results watched the effects of acetphenetidin chiefly from a decrease in heat produc- on frogs when absorbed through the tion, together with a slight increase in skin from a saturated solution. Like the heat dissipation, less marked than Mahnert, they noted a sluggishness of in the case of antipyrin. Probably the movement and loss of muscular power, delayed action of the drug depends on proceeding steadily to complete paraly- its insolubility. It should be mentioned, sis, with final cessation of the heart however, that certain authors describe beats. In addition, they found that the its effect as being more prompt, and motor nerves and the muscles, though comparable with that of acetanilide. soaked in saturated acetphenetidin so- With regard to the manner in which lution, continued responsive to electric the antipyretic eft'ect is produced, the stimulation throughout the period of ac- prevailing belief is that it depresses the tion of the drug, and even after death, heat-regulating centers. and concluded, therefore, that the loss As Analgesic. — Acetphenetidin is of reflexes and paralysis observed had considered to exert a sedative effect been of spinal origin. They ascertained upon the nervous system. Its anodyne that doses of 0.5 Gm. per kilo, injected influence is more marked than that of i"to the jugular vein of a dog, caused acetanilide or antipyrin. It is believed c^eath from paralysis of respiration, to depress the nerve-centers, in common Local applications of acetphenetidin with the other antipyretics, but it has have some analgesic effect, probably also some action on the sen- On the Circulation. — Conflicting sory nerves, since it frequently relieves views have been advanced by different neuralgic pain without giving evidence observers concerning the eff'ects of the of any central depressant action by the drug on the blood-pressure. Cerna and production of drowsiness or mental Carter found that, in moderate doses, it apathy. caused a rise of the arterial pressure by Injected into animals, large doses of directly stimulating the heart's action, acetphenetidin are required before its and also, probably, the vasomotor sys- effects on the nervous system appear, tern, while in large doses it decreased Using doses of 0.5 to 1 Gm. per kilo of the pressure, chiefly by its influence on body weight in rabbits, Mahnert ob- the heart. They also state that acet- served merely a muscular weakness, phenetidin tends to increase the pulse lasting a few hours, which he ascribed rate, mainly by cardiac stimulation, and to a depressing action on the spinal possibly, also, by influencing the cardio- cord. With doses of 3 Gm. per kilo he accelerator apparatus, while later, es- obtained a short period of spinal excita- pecially with large doses, it decreases tion, followed by one of complete motor it primarily by stimulating the cardio- and sensory paralysis, with loss of re- inhibitory centers, and later b) depress- flexes and early death. In frogs the ing the heart. Ott and H. C. Wood, preliminary spinal excitation may be Jr., on the contrary, assert from their such as to produce convulsions. In experiments that acetphenetidin does mammals convulsions produced by the not influence the blood-pressure. Mah- Hntipyretics may be of cerebral, spinal, nert considers the drug to be antago- 240 ACETPIIENETIDIX (SAJOUS). nistic to strychnine in its physiological action, large doses producing paralysis of the cardiac and respiratory centers. In the early stage of its action, however, it is believed to stimulate these centers for a time. On the Blood. — Alterations in the blood are much more rarely caused by acetphenetidin in moderate doses than by acetanilide. The formation of met- hemoglobin has, however, been ob- served in a few cases. According to Cushny, this untoward result is due to the action of para-amidophenol, into which the drug is gradually decomposed in the organism. Cerna and Carter were unable to produce methemoglobi- nemia in their experiments on animals. Acetphenetidin is said to have a slightly stimulating influence on the sweat-glands, which is not possessed by the other antipyretics. Elimination. — Acetphenetidin is be- lieved to be eliminated chiefly in an al- tered condition, losing its acetyl radicle in transit through the organism, and ap- pearing in the urine as glycuronates of phenetidin (Cushny). The gastric and pancreatic juices being without influ- ence on the drug {)i vitro, F. IMiiller be- lieves that the decomposition must oc- cur after it has been absorbed. Accord- ing to Gueorguievsky, the elimination by the urine begins in twenty minutes and proceeds rapidly. Perchloride of iron added to this urine causes a Bur- gundy red color to appear. Acetphe- netidin may also be eliminated in part by the skin, since Hirschmann not infre- quently found large numbers of crystals precisely similar to those of the drug on the skin of persons to whom it had been administered. UNTOWARD EFFECTS AND POISONING.— H. C. Wood states that no symptoms are produced by the therapeutic dose of this drug. Even large doses of it have been given so often without markedly un- pleasant results that, in contrast with acetanilide and antipyrin, it has fre- quently been described as non-toxic. ^Massive doses, however, and even mod- erate doses in certain susceptible indi- viduals, have been known to cause un- toward effects similar to those of the other coal-tar antipyretics. The most commonly observed of these have been profuse sweating, somnolence, lassitude, sometimes accompanied by nausea, ver- tigo, or chilliness. In more severe cases there have occurred cyanosis, beginning and most marked in the face, lips, and finger-tips, then becoming general ; pros- tration, vomiting, palpitation, dyspnea, anxious expression, followed by col- lapse, which occasionally is fatal. The blood may be darkened by the forma- tion of methemoglobin. The urine has been found to contain blood (Kronig). In a case reported by Ilollopeter three doses, of 7 grains each, of phenacetin sufficed to produce in a woman severe precordial pains, great dyspnea, general lividity, somewhat dilated pupils, and collapse, with unconsciousness ; recovery took place after a week. Cutaneous eruptions, usually urticarial, are some- times caused, though less frequently than by antipyrin. As with acetanilide, the onset of the symptoms is frequently sudden and unexpected, the patient hav- ing previously borne repeated doses without harmful efifect. A girl of 16j^ years, in goo(^ gen- eral health, but having a headache and feeling that she had taken cold, took 2 headache tablets and went to bed. About an hour and a half later her lips and face began to grow blue, and a physician was sent for. Re- sponding at once, he found the girl with pronounced cardiac weakness ACETPHENETIDIN (SAJOUS). 241 and edema of the lungs. Before any remedy could be administered she. died. The tablets she had taken, labeled "Danbury's headache tablets," were subsequently found on exami- nation to contain acetphenetidin. G. L. Tobey (Mo. Bull., State Board of Health of Mass., Jan., 1908). Of 70 cases reported by 41 observ- ers in the literature from 1887 to 1907, 3, or 4.2 per cent., terminated fatally. Sixty-three of the 70 cases were reported during the years 1887- 90, i.e., in the period just following the advent of acetphenetidin as a medicinal agent, when the drug was used freely in asthenic as well as sthenic affections. The most promi- nent ill effect was general systemic depression, which was present in 38.5 per cent, of the cases. In 17.1 per cent., it amounted to actual col- lapse. Cyanosis was reported in 34.3 per cent, of the cases, skin affections of various kinds in 30 per cent., dysp- nea in 14.3 per cent., and disturbances of the renal function in 10 per cent. Kebler, Morgan, and Rupp (U. S. Dept. of Agricul., Bureau of Chem- istry, Bull. Xo. 126, July 3, 1909). Treatment of Acute Poisoning. — No special reference to this subject having been found in the literature, we can only recall the plan of treatment used for poisoning by the other coal-tar deriva- tives, the toxic effects of which are iden- tical. Stimulants to the circulation and respiration, such as strychnine, atropine, aromatic spirits of ammonia, ether hypodermically, and digitalis; saline solution by enteroclysis or hy- podermoclysis, etc. The application of heat to the body should never be neglected in cases of collapse. Arti- ficial respiration is always valuable, and inhalations of oxygen may be re- sorted to as an ultimate measure. CHRONIC POISONING.— While not as frequent as chronic acetanilide poisoning, chronic acetphenetidin poi- soning is nonetheless fairly common. The symptoms show a great similar- ity to those produced by the habitual use of acetanilide, consisting chiefly of nervous and digestive disturbances, a cvanotic coloration of the skin, ane- mia, and weakened heart action. Instances of chronic poisoning have l)een reported by several clinicians. J. S. Davis observed a case in a woman, pre- viously "a healthy, buxom country girl,'* who had been addicted to the acetphene- tidin habit for about seven months, in- gesting from 15 to 20 grains daily. The habit was found out by her husband when her supply of the drug gave out and the local pharmacist also ran out of a supply temporarily. Violent convulsive and hys- terical seizures appeared, and continued until acetphenetidin had been obtained for her. The pulse rose to 170 and became feeble; respiration, 30, spasmodic; pupils widely dilated; pallor and cold perspira- tion. The patient had over a dozen con- vulsions and vomited freely. Examina- tion subsequent to the attack showed some anemia, poor complexion, weak cir- culation, pulse 124, sleep restless and troubled, digestion impaired, occasional vertigo. From collective reports of cases it would appear that toxic manifesta- tions are somewhat less likely to de- velop when acetphenetidin is taken habitually than when acetanilide is the drug used. In the replies of 400 physicians to a set of questions sent out by the Bureau of Chemistry of the U. S. Department of Agriculture, 112 in- stances of the acetanilide habit were reported, 7 of the antipyrin habit, and 17 of the acetphenetidin habit. The number of cases in which ill effects were observed from the use acetanilide was 85, from antipyrin 2, and from acetphenetidin 7. The chief symptoms observed from the habitual use of these drugs were: Xervous depression, 44 cases; cya- nosis, 27; cardiac depression, 18; ane- mia, 15; dyspnea on exertion, 8; in- somnia, 4; constipation, 3; edema, 2; 1—16 242 ACETPHENETIDIN (SAJOUS). increased headache, 2; icterus, 1; muscular twitchings, 1 ; loss of sex- ual power, 1. In 5 of the cases of acetphenetidin habit protracted ill effects were noted, as compared with 32 instances in case of acetanilide and 2 instances in case of antipyrin. The chronic symptoms oftenest noted were anemia, general debility, nervousness, and weak and irregular heart action. Kebler, Morgan, and Rupp (U. S. Dept. of Agricul., Bureau of Chemistry, Bull. No. 126, July 3, 1909). Treatment of Chronic Poisoning. — The measures required upon vvitii- drawal of the druc^ will ii^encrally coiu- prisc the use of stimulants, saline lax- atives, and codeine. — tlie latter used with caution in amounts just sufficient to mitii^'ate pain and favor sleep (v. Treatment of Chronic Acetanilide Poisoning"). THERAPEUTICS. — As Antipy- retic.— .Vcctphenclidin is generally con- sidered the safest of the coal-tar an- tipyretics. Its effect in reducing tem- perature is marked ; as previously stated, its action begins in about thirty minutes and reaches its maximum in three to four hours. According to Heusner, 1 Gm. (15 grains) of this drug is the equal in antithermic power of 0.5 Gm. (7^ grains) of acetanilide, and 2 Gm. (30 grains) of antipyrin. The relative infrequency with wliich it causes cya- nosis, depression, and other unpleasant or dangerous effects recommends its general use as an antipyretic in prefer- ence to the older coal-tar remedies if used at all. The employment of anti- pyretics other than hydrotherapy and other external measures is decidedly on the wane, however, in the hands of competent clinicians. Exception to this is probably only to be made where prompt reduction of fever is required, as in cases of hy- perpyrexia ; here acetanilide, whether used in conjunction with hydrothera- peutic measures or not, may prove more effective than acetphenetidin. It is be- lieved, however, that the effect of the latter drug is more lasting than that of acetanilide ; the greater tendency of which to depress the circulatory and respiratory organs should also be re- membered. As stated above, however, the use of antipyretics in the various forms of fever is now deemed inadvis- able by most authorities. Moreover, these agents, by causing the temperature records to lose their characteristic fea- tures, may imi)air their value for diag- nostic and prognostic purposes. The alleged prejudicial influence, on the other hand, that chemical antipyretics have been said to exert on tlie sub- stances of the blood-serum that antag- onize disease has been shown not to exist, at least in the case of the agglu- tinating bodies of typhoid serum (Soll- mann). When delirium is present in fever, the mild narcotic action exerted by the coal-tar antipyretics, especially acetphenetidin. may prove useful. As an Analgesic. — Phenacetin is chiefly of value for the relief of pain, especially of pain of the neuralgic type. In pains due to gross inflammations or deep-seated distress, the result of or- ganic disease of viscera, morphine is far more effective than phenacetin. But in pains due to nervous disorders, es- pecially neuralgia and neuritis, and in various forms of headache, acetpheneti- din has come to be considered almost as a specific. In hemicrania, in head- ache due to eye-strain or insufficiency of certain of the extraocular muscles, in intercostal neuralgia, sciatica, gastral- gia, and in the pains of tabes dorsalis, acetphenetidin frequently affords con- siderable relief. ACETPHEXETIDIN (SAJOUS). 243 The manner in which this drug, in common with other coal-tar antipyret- ics, acts in reUeving headache has not yet been definitely ascertained. Accord- ing to Brunton, headache is associated with and caused by what he terms a "colic" of the arteries of the head, the peripheral vessels being contracted and the central vessels dilated; the drug would presumably give relief by over- coming this abnormal condition of the cephalic arteries. E. Weber has re- cently demonstrated experimentally in dogs whose brain had been exposed that coal-tar drugs cause constriction of the vessels on the surface of the cerebrum. It is well kno\vn, moreover, that caffeine, an undoubted vasoconstrictor, when combined with the coal-tar drugs, greatly assists their analgesic action in headaches. Hence it would seem as if the relief given in these cases were due, in some way. to a modification in the caliber of the vessels. In acute rheumatism, acetpheneti- din has been found useful as an anal- gesic in doses of 3 to 8 grains (0.2 to 0.5 gram), given every four hours. A valuable combination is 4 grains each of acetphenetidin and salol, given three or four times daily. Eldredge counsels the administration of acetphenetidin in pow- der and salicylic acid in solution, the dose of each being regulated according to the patient's susceptibility and the severity of the attack. In cases with cardiac complications, he claims not to have observed any depressing action on the heart when the drug was given to reduce fever. Hirschfelder noted spe- cially the fact that sometimes a hyp- notic action seemed to be produced. In subacute rheumatism and in lumbago and other rheumatic muscular pains, the drug is also frequently effective. In gonorrheal rheumatism, acetphe- netidin was found by Eldredge to act well when given with potassium iodide and sodium salicylate. In influenza, acetphenetidin has be- come a favorite remedy. The pains in the head, back, and limbs are relieved, and the fever reduced. The drug may be given alone in powder form, or com- bined with other remedies, e.g., quinine. In this disease, essentially an asthenic disorder, it is important that the anal- gesia be secured with the least possible degree of general depression ; hence acetphenetidin should always be given the preference over its more depressing congeners — acetanilide and antipyrin. Acetphenetidin and other coal tar preparations have been successfully employed in the treatment of mi- graine and in neuralgia. Pharmaco- logists assume that these results are obtained by a chemical blocking of the nerves that mediate sensations of pain, said blocking taking place presumably in the region of the thalamus. So effi- cient have these products proved in wisely selected cases, that their use seems at present to be justifiable, des- pite their undeniable ulterior eflfects, many of which are sometimes exceed- ingly alarming and some of which have resulted in fatalities. In using these preparations it should be strictly borne in mind that the obvious benefits se- cured in neuralgia and migraine are pal- liative only; the drugs are in no sense curative, even though their power to give grateful alleviation may readily continue until the provocative cause of the distress has more or less completely disappeared. The aim should be to ascertain the source of the neuralgic toxin and eliminate it. One should select the less poison- ous of the several products, acetphe- netidin for example, and administer it in the smallest adequate doses. 0.2 to 0.6 Gm. (3 to 10 grains) being usu- ally sufficient. A. D. Bush (N. Y. Med. Jour., Jan. 15, 1916). 244 ACETYLENE. In whooping-cough, acetphenetidin diminishes the severity and freqtiency of the paroxysms. In children, 1 or 2 grains (0.06 to 0.013 gram), given three or four times daily, are generally suf- ficient. Chorea has also heen treated with acetphenetidin. Like the other coal- tar drugs, acetphenetidin exerts a not inconsiderable effect on the motor func- tions and refiex action, as well as on general sensibility. Hence the fact that it sometimes proves useful in this dis- order. Insomnia, the result of overwork or general nervous excitability, may yield to acetphenetidin. Kiernan reported having seen it bring on sleep in persons suffering from insomnia due to simple exhaustion. In view of the possible serious depressive effects from an over- dose, the likelihood of a drug habit be- ing formed, and the fact that much safer and better hypnotics are available, it seems doubtful whether the use of acetphenetidin for this purpose should be encouraged. The same is probably true of the use of acetphenetidin in the initial stage of pneumonia, in which it has been em- I)loyed to relieve distress, bring on sweating, reduce fever, and favor sleep. If the drug is used at all, it must surely be withdrawn as soon as the patient begins to show pronounced general de- pression and signs of lowered circula- tory activity. In pleurisy acetpheneti- din has likewise been used to relieve the pain of the initial stage. The first stage of acute coryza may be shortened by giving a few doses of acetphenetidin, which will not only pro- mote sweating and lower the tempera- ture, but also relieve the unpleasant accompanying sensations. A powder containing 5 grains (0.3 gram) each of acetphenetidin and salol, together with 1 grain (0.06 gram) of citrated caffeine, may be administered every three hours for 3 doses with advantage. In diabetes mellitus acetphenetidin, in common with other coal-tar drugs, has been prescribed, generally with but temporary benefit. Local Uses. — Acetphenetidin is sometimes used externally for its anal- gesic and antiseptic properties. Dusted in finely powdered form on the raw sur- faces of ulcerations of various kinds, it not only relieves pain, but favors the development of healthy granulations, thereby hastening the healing process. Because of its low degree of solubility in water, as compared with antipyrin and acctanilide, the likelihood of the absorption of a toxic amount of acet- phenetidin from open surfaces is somewhat less than with the above- mentioned agents. Nevertheless, this danger should always be kept in mind, and the external use of the drug confined to lesions covering a small area only. C. E. DE M. S.vjous AND L. T. DE M. Sajous, Philadelphia. ACETYLENE.— When calcium car- bide (CaC2) is brought in contact with water, acetylene gas is formed. Being capable, when ignited, of furnishing a de- gree of light far superior to that of ordi- nary gas, acetylene has in recent years been considerably used as an illuminant. When prepared from pure calcium carbide and purified by liquefaction, it has a pleas- ant ethereal odor and can be breathed in small quantities without giving rise to ill effects. Impure gas, prepared from coal or impure lime, may contain calcium sul- phide and phosphide, and the acetylene prepared from it may then have a very unpleasant odor. Acetylene Poisoning. — Acetylene may be fatally poisonous when present in propor- ACIDITY OF THE GASTRIC CONTENTS. 245 tions as high as 40 per cent, by volume, as shown by Grehant, Berthelot, and Mois- sant. A mixture of 20 volumes of acety- lene— prepared from calcium carbide, 20.8 volumes of oxygen, and 59.2 volumes of nitrogen — was breathed by a dog for thirty-five minutes without any marked disturbance, and 100 c.c. of the blood were found to contain 10 c.c. of acetylene. With 40 volumes of acetylene, the proportion of oxygen remaining the same, a dog died in less than an hour, owing to failure of the heart's action, and 100 c.c. of blood con- tained 20 c.c. of acetylene. With 79 vol- umes of acetylene and 21 volumes of oxy- gen the poisonous effects were still more strongly marked. The poisonous action of acetylene itself is feeble when the blood is at the same time supplied from the air with the usual amount of oxygen. In other words, acety- lene inhaled in the open air is but slightlj-^ harmful. Brociner found that 100 volumes of blood dissolve about 80 volumes of acetylene; the solution shows no charac- teristic spectrum, and is reduced by am- monium sulphide as readily as ordinary arterial blood. If any compound of acety- lene and hemoglobin is formed, it is very unstable, and is not analogous to carboxy- hemoglobin. In a closed room, however, where the oxygen is not kept up to the normal stand- ard, when the accumulation of a foreign gas would prevent the constant renewal of air through window and door interstices or open chimneys, and where the products of respiration w^ould be allowed to accu- mulate, it would quickly prove mortal by paralyzing the respiratory function. Mosso and Ottolenghi found experimen- tally that acetylene has considerable toxic power. One pint of the pure gas caused severe symptoms of poisoning in dogs, and even when mixed with air (20 per cent.) it proved fatal after an hour. If the gas was administered rapidly, the animal re- covered when placed in the open air, but if given slowly this did not occur, and the animals died. Thomas Oliver has shown that a mixture of air and acetylene commences to be ex- plosive v/hen it contains 5 per cent, of acetylene, whereas it requires the presence of 8 per cent, of coal gas to make a similar mixture explosable. If a rabbit is placed in a bell-jar into which ordinary air and acetylene are pumped, the animal seems for a long period to experience very little inconvenience. It is not until ordinary atmospheric air is excluded and only acety- lene admitted that symptoms gradually and slowly develop. After a more length- ened exposure to acetylene than that which is necessary for coal gas the animal becomes intoxicated, it falls over on its side apparently profoundly asleep, and, while all through the experiment its breathing has been somewhat short and rapid, stupor steals over the animal ap- parently painlesslJ^ A few inhalations of atmospheric air are sufficient to restore to the animal all its faculties. Should in- halation have been pushed further and the animal have been very deeply asphj'xiated, death may ensue, cyanosis, hitherto ob- served, being rapidly replaced by extreme pallor. Treatment of Acetylene Poisoning. — That fresh air should at once be given the patient need hardly be mentioned. The patient should be removed from the poisoned atmosphere into a well-ventilated room and artificial respiration practised. Hypodermic injections of strychnine and digitalis should be administered while oxygen is sent for. This gas should be inhaled as soon as practicable, while arti- ficial respiration is continued with vigor, the patient being simultaneously rubbed. Rectal injections of warm coffee are also useful. Hypodermoclysis, with epinephrin or adrenalin 1 : 1000 solution introduced drop by drop into the saline solution by pushing the hypodermic needle into the rubber pipe, is indicated in all cases of severe poisoning bj' the gas. In all such cases the efforts of the physi- cian should be kept up a long time, the respiration and pulse being unreliable guides as regards the presence in the sys- tem of sufficient life to render resuscitation possible. S. ACIDITY OF THE GASTRIC CONTENTS, TESTS FOR.— while the acidity of normal gastric juice is due mainly to the presence of hydrochloric acid, departures from the normal proportion of this acid in the gastric contents have been 246 ACIDITY OF THE GASTRIC CONTENTS. found to accompany with sufficient frequency- certain disorders to facilitate the recognition of these disorders. Thus, a proportion of hydrochloric acid of O.lS to 0.3 per cent, represents the acidity found under normal conditions, i.e., euchlorhydria, but an ex- cess of acid, hyperchlorhydria, is common in gastric ulcer, gastroptosis, hysteria, tabes, and other disorders. Hypochlor- hydria, a deficiency of hydrochloric acid, also accompanies various disorders, espe- cially gastric cancer, neurasthenia, anemia, chronic gastritis of long duration, gastric neuroses, and certain diseases of the pan- creas, while achlorhydria, absence of hydro- chloric acid, is found in advanced cases of the same disorders. Again, the fact that hydrochloric acid is necessary to peptic digestion, while acting as a powerful anti- septic to the ingested foodstuffs, further indicates the practical importance of ascer- taining accurately the acidity of the gastric contents. To obtain accurate information, it is necessary to administer a test-meal con- taining a definite quantity of foodstuffs, and to leave the latter in the stomach a definite time. Test-meals. — Those described are gen- erally given preference: — The Ewald-Boas breakfast consists of 1 roll weighing about 35 Gm. (9 drams) and a large wineglass of 300 Gm. (10 ounces) of water. This meal should be taken early in the morning on an empty stomach, the bread being eaten slowly and the water sipped while this is done. At the end of one hour, 20 to 60 c.c. (5 to 10 drams) of the meal should be withdrawn from the stomach in the manner indicated below. The Leiibe-Ricgel test-meal consists of beef soup, 400 c.c. (12 ounces); beefsteak finely chopped, 200 Gm. (6 ounces); wheat bread or potato, 50 Gm. (1.6 ounces), and water, 200 Gm. (6 ounces). The gastric contents should be removed at the end of four hours. The Salzer method includes two meals: The first consists of 30 Gm. (1 ounce) of lean roast beef chopped very fine ; milk, 250 c.c. (8 ounces); rice, 50 Gm., and 1 soft-boiled egg. The second meal, given four hours later, is an Ewald-Boas break- fast, described above. At the end of five hours after the first meal, that is to say. one hour after the second, the gastric con- tents is withdrawn. The Salzer test affords, in addition to the opportunity of ascertaining acidity, that of determining the motility of the gastric muscles; for if particles of meat of the first meal are still present at the end of five hours, the propulsive activity of the stomach wall is deficient. Withdrawal of Gastric Contents. — This, the next step of the examination, is car- ried out with the aid of a flexible red rub- ber tube about a yard in length, the catheter-like end of which is provided, a short distance above the tip, with a fenes- tra or opening. It is an ordinary stomach tube the upper end of which is funnel- shaped. About 2 feet above this end is a mark which, when the tube is introduced sufficiently far, i.e., when its tip reaches the bottom of the stomach, corresponds with the incisor teeth of an adult. The patient's clothing being protected with a towel tied round his or her neck, the tube, previously warmed by being placed in a bowl of warm wat r and lubri- cated with glycerin, is introduced, i.e., passed down the esophagus. This is done readily by pushing the end of the tube gently into the latter, over the epiglottis, while the patient swallows, and as often as he does so. In some cases, especially the first time, the procedure may causfc gagging, but this can be avoided by pass- ing the tube on one side of the epiglottis, i.e., in either pyriform sinus. The sensi- tive surface of the pharynx is thus avoidea. To withdraw the gastric contents several ways are available. The easiest is to de- press the external end of the tube as soon as the latter is in situ, and request the pa- tient to lean forward and cough a few times or contract his abdominal muscles. An essential point, however, is that the (clean) bowl in which the gastric contents is to be collected must be considerably below the level of the patient's stomach, i.e., between his knees, so as to obtain the benefit of siphonage. The expulsion of the gastric contents is facilitated by press- ing on the stomach while the patient is coughing or contracting his abdominal muscles; it is further aided by having him lie down on a lounge, the bowl being placed on the floor. It is not necessary to ACIDITY OF THE GASTRIC CONTENTS. • 247 empty the stomach, a couple of table- can be used in the same manner. Its yel- spoonfuls (about 30 c.c.) sufficing for all lowish-brown alcoholic solution turns red purposes. in the presence of both hydrochloric acid Various pumps, aspirating bulbs, etc., and lactic acid; but the former can be have been invented to deplete the stomach, differentiated by spreading a few drops of but they entail the use of parts that are a saturated solution in a porcelain dish, difficult to clean properly, and expose the and adding thereto an equal quantity of gastric mucosa to the evil effects of direct the gastric fluid. On mixing them and suction by the tube. Moreover, compli- heating them gent'y, blue and lilac stripes cated instruments tend to increase the (formed by hydrochloric acid only) appear, timidity of the patient, which, at best, is An extremely delicate test, which will sometimes difficult to overcome. Briefly, detect 1 part of hydrochloric acid in the above-described "simple expression 20,000 parts of water, is Gunzbiirg's, whose method" is, on the whole, the most satis- reagent consists of: — factory. t, r,, Contraindications to the Use of the ^ Phloroglucin 2Gm. (30gr.). c . T, , T ■ <• Vamlhn IGm. (15gr.). Stomach Tube.— In a certain proportion of Absolute alcohol 30 c.c. (1 oz.). cases, however, even the use of the simple stomach tube may prove dangerous. They It should be kept in a dark bottle. By are: cases of advanced cardiac disorder; adding a few drops of this reagent to the advanced arteriosclerosis, especially if gastric filtrate and allowing the mixture there is a history of cerebral hemorrhage to evaporate to dryness, a beautiful rose- or "slight stroke"; elderly persons of red tinge is obtained if free hydrochloric apoplectic build. In either of these the acid is present. tube may cause a sudden reflex rise of the To Ascertain the Total Acidity. — The blood-pressure and rupture of any diseased easiest method is to add 1 drop of a 1 per vascular tissue. A history of recent hema- cent, solution of plioiolphthalcin to 10 c.c. temesis or of bloody or tarry stools is (2/4 drams) of the gastric fluid, after also a contraindication, since the bleeding filtering the latter, and neutralizing the may be due to gastric ulcer or cancer, mixture by a given quantity of decinormal which the extremity of the tube might solution (about 30 grains to the pint— 2 readily abrade, and thus cause renewal of Gm. in 500 c.c. of distilled water) of the hemorrhages. Advanced tuberculosis, sodium hydroxide. The technique of the marked emphysema, pregnancy, and ex- procedure is as follows: Place 10 c.c. of treme debility are also recognized as con- the filtered gastric fluid in a beaker, and traindications. add thereto 2 drops of phenolphthalein Determination of Free Acids. — The mere solution. Then add the decinormal sodium presence of any free acid, hydrochloric, hydroxide solution from a graduated bu- lactic, etc., can readily be determined by rette (mixing with a glass rod) until a using paper previously dipped in a solu- permanent red or reddish-pink color ap- tion of Congo red and dried. This turns pears, which means complete neutraliza- blue in the presence of free acids, but does tion. Now, the number of c.c. (say 4 or not identify one acid from another. 45) of sodium hydrate solution necessary To identify hydrochloric acid, the best to obtain the latter, as shown by the reagent is probably the dimethylamidoaso- graduated burette, with a naught to the benzol. It may be used in 0.5 per cent. right of this figure (making 40.0 or 45.0 of solution or in absorbent paper allowed to the above figures), will represent the per- dry before using. The yellow color of centage of total acidity, either becomes reddish pink in the pres- A watery solution of Congo red may be ence of hydrochloric acid. This test fur- used instead of phenolphthalein. As we nishes an inkling as to the degree of have seen, free hydrochloric acid in the acidity due to the latter, for the reddish- gastric fluid or chyme changes the red pink color becomes much deeper in pro- color to blue. If, now, decinormal sodium portion as the percentage of acid is great. hydrate solution (vide supra) is slowly Tropeolin is another good reagent which added to the mixture until the Congo red 248 ACNE (STELWAGON). is restored, the number of cubic centi- meters of the sodium hydrate solution re- quired to obtain this result will represent the amount of free hydrochloric acid. Lactic acid, which suggests the presence of cancer or dilatation, being contained in all bakery products, in meats as sarco- lactic acid, sour milk, sauerkraut, and sour gherkins, a special meal is necessary lo eliminate from the test the acid due to n Strauss's separating funnel for lactic acid test. foods. A bowl of soup prepared with Knorr's oatmeal, rendered palatable by adding common salt, suffices for this pur- pose. Uffelmann's reagent may then be used. It is composed as follows: — B Solution of carbolic acid (4 per cent.) 10 c.c. Distilled water 20 c.c. Official neutral ferric chloride solution 1 drop. This should be prepared fresh for each test. Its amethyst-blue color will be turned to canary yellow when added to the gastric filtrate. A quantitative estimation of lactic acid may be obtained by Strauss's method. "A separating funnel (shown in the annexed cut) with marks at 5 c.c. and 25 c.c. is filled to the first mark with gastric juice and then to the second with ether. After thoroughly shaking, the fluid is allowed to flow out to the first mark (5 c.c), then filled with water to the second mark (25 c.c). Two drops of a 10 per cent, solution of iron chloride are then added. A beautiful green color appears in the presence of amounts exceeding 0.5 per mille." (Lenhartz-Brooks.) Butyric acid and other fatty acids, on boiling the gastric filtrate, emit a charac- teristic odor. They also turn yellowish brown in the presence of Uffelmann's solu- tion, just described. Another test is to shake the gastric product (unfiltered) with acid-free ether, and then allow the latter to evaporate. On adding calcium chloride to a watery solution of the residue, the butyric acid forms oil droplets with the characteristic odor of the acid. Acetic acid also emits a characteristic odor, that of vinegar. A small quantity of gastric filtrate, say 10 c.c, is treated with ether as above. The residue being dis- solved in a little water and neutralized with a solution of sodium carbonate, a couple of drops of a very dilute solution of ferric chloride are added. The filtrate then becomes dark red if acetic acid is present. Or a few drops of sulphuric acid and alcohol may be added to the same neutralized residue; on heating, the latter then gives off the characteristic vinegar- like odor of acetic acid. S. ACIDOSIS. TION. See AuTOiNTOXicA- ACNE.— DEFINITION.— Acne is characterized by the presence, usually on the face, of small elevations or nodosities varying in size from a pinhead to a pea. These elevations, or pimples, are also present on the back, shoulders, and chest in many cases. SYMPTOMS.— The elevations are conical or hemispherical, and, as a ACNE (STELWAGON). 249 rule, in the earliest stage of the lesion somewhat painful, especially upon pressure. In most of the lesions there is a distinct tendency to suppurative change. In the center of the lesion a whitish-yellow spot forms where the pus raises the epidermis. In from three to ten days, or even longer, the lesion breaks and a small amount of pus is discharged. At other times the pus dries to a thin crust, or occasion- ally the contents, especially in slug- gish lesions, are absorbed. A red elevation is left which gradually flat- tens out, leaving a brownish stain, wdiich eventually disappears. The surrounding skin is frequently oily and shiny. Small, sluggish, abscess- like lesions, and tumors as large as a pea or a small nut, formed by reten- tion cysts of sebaceous glands, are sometimes seen ; they may gradually work to the surface or may persist for months and finally disappear or form hard spherical indurations by retrac- tion and inspissation of their contents. Scarring, usually consisting of small, white, cicatricial depressions, is to be seen as a consequence in some cases. In the majority of cases, however, permanent marks are not left. The regions most affected in acne are the face, shoulders, and anterior and pos- terior aspects of the shoulders. Occa- sional cases are observed in which the back, extending as far down as the sacrum, is the chief seat of the disease. In rare instances (acne cachecticorum, acne scrofulosorum, and acne medi- camentosa) the eruption may be more or less general. VARIETIES.— There are several varieties of lesion observed in acne, one kind of which is apt to predomi- nate, and this has given rise to the so- called varieties of the disease. Acne vulgaris, or acne simplex, is, by far, the most common clinical type. The lesions are usually of a mixed character, consisting of blackheads, pinhead- to pea-sized papules, papulo- pustules, and pustules. Each lesion may in its beginning have a small, red areola. There is also slight pain upon pressure. The lesions are rapid in evolution, running a course in several days to a week. As in all types, they are discrete and isolated. The term "acne pap]tlosa" is given to a not uncommon type in which the lesions are usually small and show but little disposition to reach the pustular stage, disappearing by absorption or by desiccation and exfoliation. Acne punctata might be termed mi- nute papular, the lesions being, for the most, pinhead in size, with a central comedo, or blackhead. Acne pnstnlosa is another type in which the lesions go rapidly into the pustular stage, the eruption appearing, for the most part, to be made up, almost entirely, of pustules. In size they vary from a large pinhead to a large-sized pea. Acne indnrata, or '^tuberculosa'' is a form of the eruption in which the lesions tend to be closely crowded here and there and in such places, and also with single lesions, the underly- ing base becomes hard, inflamed, and indurated, being also somewhat deep- seated. In acne phlcgmonosa the inflamma- tory and suppurative process begins deep down in the sebaceous gland, forming veritable small dermic and intradermic abscesses, usually with but slight tendency to break through the surface. Acne cachecticorum characterizes an acneic eruption, more or less general. 250 ACNE (STELWAGON). occurring in weak, cachectic individ- uals; the lesions are livid, indolent, violet-red papulopustules of moderate and large size and of slow evolution, leaving, as a rule, small cicatrices. Acne scrofulosorum is really a variety of the last named, — acne cachecti- corum, — occurring in those of dis- tinctly strumous or tuberculous tem- perament. Acne artificialis sen medicamentosa is a form of acneic eruption produced by the ingestion of certain drugs, as the iodides and bromides, and also by the external applications of certain reme- dies, such as tar, the paraffin oils, etc. "Acne atrophica" is a name given to those cases of acneic eruption which tend to leave depressed scars. Tiiis probably occurs most frequently in those cases in which the lesions are sluggishly papular or papulopustular, the lesions disappearing by absorption or crusting and leaving behind small, punched-out cicatrices. Acne hypertrophica is really the op- posite of the last-named variety, and occurs in about the same kind of cases, small, whitish, connective-tis- sue, pinpoint or small-pea sized pro- jecting hypertrophies marking the sites of the lesions. It is rare. ETIOLOGY. — Acne begins usually near puberty, when the pilar system is more actively developing, and the functions of the sebaceous glands like- wise ; and is more frequent among patients with digestive troubles, con- stipation, dilatation of the stomach, menstrual irregularities, the strumous diathesis, possibly the arthritic di- athesis, and disturbances of the nerv- ous system. The etiological participation of gas- trointestinal disorders in acne vul- garis are receiving due attention. While the acne bacillus is generally recognized as the direct cause of acne vulgaris, a number of associated conditions probably act as predispos- ing factors, among which gastrointes- tinal abnormalities seem of special importance. They investigated the problem in 30 cases by means of fluoroscopic examination of the gas- trointestinal tract, test meals, and analyses of the gastric contents. It was found that 93 per cent, showed gastric abnormalities and 70 per cent, intestinal abnormalities. The most common gastric lindings were hyper- acidity, 48.1 per cent.; retention. 36.6 per cent.; atony, 2)2).2> per cent., and ptosis, 40 per cent. The most com- mon intestinal findings were cecal stasis, 46.6 per cent.; ptosis of the colon, 36.6 per cent., and right lower quadrant adhesions, 23.3 per cent. Clinically, 62.3 per cent, of the cases gave evidence of gastric disturbances and 40 per cent, were constipated. None of the cases examined gave en- tirely normal gastrointestinal find- ings, and 60 per cent, showed abnor- malities which were of such a nature as to permit gastric and intestinal stasis, followed by toxic absorption. L. W. Ketron and J. H. King (Jour. Amer. Med. Assoc, Aug. 26, 1916). [The confusion concerning the patho- genesis of acne is due, in my opinion, to the fact that the ductless glands are over- looked in tile morbid process. As I pointed out in 1914 before the Manhattan Dermatological Society of New York, a close relationship suggests itself when these structures are accepted as active participants in the morbid process. At puberty we encounter the period when the thymus has ceased to furnish its nucleins. Many of the disorders of ado- lescence may be traced to this cause. De- velopment has ceased, and the other or permanent ductless glands whether ready or not, must sustain the life process with- out the thymus. The pancreas, thyroid and adrenals maintain not only the nutri- tional processes of the body, oxidation and metabolism, but simultaneously its defen- sive process. When we realize that they do this while carrying out the catabolic ACNE (STELWAGON). 251 phase of metabolism, and as a part of this process, breaking down poisons, toxins, etc., as they do normal wastes, the ap- parent complexity of the immunizing process disappears. Nevertheless, upon the integrity of these two connected func- tions depends the health of the whole. Many other facts submitted at the time suggest that acne may be due to inadequate defensive activity of the body through in- sufficiency, inherited or acquired, of one or more of the ductless glands, which not only from my viewpoint nowadays, but from that of others, take part in this gen- eral defensive process. We have indirect proof of deficient immunizing power as a cause in the effectiveness in many cases of acne, of staphylococcus vaccine, which though not specific, nevertheless provokes the formation of antibodies. Thyroid gland with pituitary or ovarian gland is also effective in hypothyroidism, especially hypothermia are discernible. When, as stated above, gastrointestinal disorders exist in the case, the result- ing autointoxication aggravates and may doubtless cause the disease, owing to the deficient antitoxic activity of the blood, due in turn to the deficient activity of the ductless glands. C. E. de M. S.] It has been also alleged without, however, substantial foundation that lesions of the genitourinary^ organs and venereal excesses may provoke the disease. Lesions may be due to mechanical irritation caused by the product of secretion remaining in the excretory canal or gland itself. Some drugs, as already stated, — such as the bromides and iodides, — are occa- sionally responsible for the eruption or an increase in an already existing eruption. Certain drugs applied ex- ternally may also provoke acneic lesions, such as tar and tar products, juniper oil, and the like. Workers in paraffin and paraffin products will not infrequently be found affected with papules and pustules, especially those of a furuncular or abscess type. The direct local exciting factor is thought, by many, to be a micro-organism, Gilchrist's observations pointing to a specific bacillus. PATHOLOGY.— In most cases the process begins by a perifolliculitis, which later on gives rise to a purulent folliculitis. It would thus seem that in some cases the sebaceous glands play but a small part in the affection. In most cases, however, when come- dones are present, the sebaceous gland itself is the starting point of the in- flammatory process. (Brocq.) Even when the focus of irritation is in the follicle, it is frequently limited to the sebaceous or sebaceous pilar}- canal. (E. Besnier, A. Doyon.) The papillae surrounding the come- done and the superficial layers of the corium are filled with blood-vessels full to repletion, and of exudation cells which are found in dilated vacuoles. (Kaposi.) If the process is very intense, the sebaceous gland may be entirely de- stroyed by the local inflammatory action, while the pilar bulba persists. (Kaposi.) The acneic process may be divided into two parts: 1. Closure of the sebaceous follicle and formation of comedo. 2. Suppuration, which only occurs in those follicles where the staphylococci aureus et albus have penetrated before the comedo formed. The complement fixation reactions tended to show the activity of colon bacilli in certain skin diseases, par- ticularly acne vulgaris, rosacea, and seborrheic dermatitis. Almost two- thirds of the cases of acne gave a positive complement fixation test with the Bacillus coU obtained from the feces of acne patients. In con- trast to this, only 15 per cent, of non- acneiform skin affections gave posi- tive reactions with this bacillus, and the non-eruptive controls which were 252 ACNE (STELWAGON). examined gave entirely negative re- sults with this organism. With a polyvalent antigen of strains of colon bacilli recovered from the feces of persons suffering from acne vulgaris, the percentage of positive reactions and the degree of complement ab- sorption were found to be higher than with the control antigens of colon bacilli from the feces of norinal persons, with the sera of persons suf- fering from acne vulgaris and sebor- rheic dermatitis. Kolmer and Scham- berg (Jour. Cutan. Dis., xxxiv, p. 166, 1916). TREATMENT.— In this connec- tion acne may be divided into (1) an irritable or inflammatory variety, in which the skin is fine and thin and easily irritated by stimulating- applica- tions, and where general treatment is important on account of the close union between the acneic eruption and various constitutional disturb- ances. Local treatment should, at first at least, be of a mild character. (2) An indolent variety, where the in- \ { ^ 1 Bacillus acnes (Harttvell and Streeter). Boston Medical and Surgical Journal. Dec, 16, 1909. DIAGNOSIS.— Acne is to be dif- ferentiated from the papular, papulo- pustular, and pustular s}'philoderms, and also from variola. Syphilis, — In the syphilitic eruption the distribution is more or less general, and more acute in its outbreak, darker hued, and occtirring occasionally with special groupings and the presence of other symptoms of the disease. Variola. — In small-pox the premoni- tory constitutional symptoms, the sud- den outbreak, the uniformity of the lesions, and many other symptoms of differential character will serve to differentiate. tegument is thick, rough, and oily, with enlarged and obstructed gland orifices, and where the most energetic local ap- plications are well borne ; here the local treatment is important. Probably most of the cases met with occupy a middle ground between these two ex- treme varieties. General Treatment. — Prophylactic measures, such as the avoidance of ex- ternal irritants, drugs and food liable to cause acne, such as coffee, tea, alcohol, pure wine, pork, veal, game too far gone, preserved fish, shellfish, fats, and cheeses. Any disorder of digestion must be ACNE (STELWAGOX). 253 counteracted in order to avoid the con- gestion of the face following meals. If the tongue is much coated and shows prominent papillae, the following is recommended : — IJ Sodium bicarb 10 grs. Ext. cascara sagr. liq 10-20 mins. Tinct. nitx vomica 7-10 mins. Peppermint water. .to make 1 fl. oz. — M. Constipation should be counteracted by gentle aperients. Any condition capable of maintaining the sympathetic system in a state of tension — such as genitourinary troubles or affections of the nasal fossae — should be eradicated if possible. If the patient is lymphatic and has a good digestion, codliver oil is of value. Anemia or chlorosis calls for the use of chalybeates with arsenic. Iron often does harm unless its constipating effect is counteracted by using aperients. When the patient is arthritic, alkalies, especially alkaline waters, are indicated. No really specific treatment is known against acne, but the following have been recommended : — Sulphur alone : powder or tablets, or with equal parts of honey. Ichthyol (Unna) : — B Ichthyol 1-2 drs. Dist. water 5 drs. M. Sig. : Fifteen to 50 drops in water, to be taken morning and evening. Arsenic bromide in weak doses, %o grain, in acne pustulosa. (Piffard.) Mercurial preparations, such as corrosive sublimate or calomel, either alone or with jalap or colocynth ex- tract, have been found useful. Summary of treatment: Prohibit cakes, pies, pastries, salt meats, fish, • and eating between meals. If anemic, give nourishing foods. Ferri citratis, 3ij: magnesii sulphatis, 3v; strych- ninae, gr. j; syr. zingiberis, 3j; aquae. 5iv. In obese, constipated, and slug- gish individuals: Potassium acetate, 3v; fl. ext. of cascara sagrada, 5ij ; A- ext. of rumex, 5iij; 1 dram in water half-hour before meals. Outdoor ex- ercise. Where comedones or pus- tules: Green soap, 5j ; resorcin, 3j; salicylic acid, gr. v; rose-water oint- ment, ^ij; to be applied at night and washed off in morning, until fair des- quamation ol)tained. Lotio all^a (po- tassium sulphide and zinc sulphate) applied at night after using hot or cold water; friction with towel. Cocks (Med. Record, Dec. 3, 1910). Acne vulgaris is caused principally by 2 factors: eating fermentable foods, and inability to prevent such foods from fermenting. Menstrua- tion, cigarette smoking, anemia, etc., are factors in acne through their in- fluence on digestion. The treatment consists in thorough mastication of the food, putting the teeth in good order, and excluding starches and sugar from the diet. Antifermentive drugs, such as aloin 0.1 Gm. (Iy2 grains), ichthyol 10 Gm. (25< drams), licorice powder q. s., to be mixed and divided into 30 capsules and 1 taken after meal, are of value. Sun- light and fresh air as well as exer- cise help a great deal. Drjing and peeling lotions help locally. Vac- cines often control the formation of pus in the lesions, but cannot, in the writer's opinion cure acne vulgaris. R. A. McDonnell (Jour. Cutan. Dis., Feb., 1917). The writer recommends in the treatment of acne, in addition to the customary local and dietetic meas- ures, suprarenal gland 5 grains (0.3 Gm.), given 3 times a day. In cases showing torpidity he ad- vocates thyroid gland ^4 grain (0.016 Gm.), thrice daily. Ovarian and testicular extracts are also com- mended. Hollander (Arch, of Derm, and Syph., May, 1921). Local Treatment. — Constitutional treatment will rarely succeed alone, while in a large proportion a local treat- ment by itself will be found efficacious. 254 ACNE (STELWAGON). The condition of the skin should be improved so that it will no longer be a suitable culture ground for the bacillus. The follicles of the skin should be emp- tied of the colonies of bacilli. The skin should be constantly kept aseptic, so that any bacilli that escape on it will be killed, and no new infection of the skin will be possible. The first indication is met by attention on the patient's general health by means of baths, diet, exercise, attention to hygiene, and lastly, drugs. The follicles are emptied by the use of the curette, the acne lancet, and the comedo expressor. The best local ap- plication is sulphur, preferably in the form of the old lotio alba, the formula for which is : Zinc sulphate and potas- sium sulpheret, of each, 5i-ij ; rose water, q. s. ad 3iv. This is to be shaken up before usinji:. Resorcin is also use- ful, as well as sulphur soap. The use of the Rontgen ray should be limited to intractable cases, and requires great caution to prevent doing harm. G. T. Jackson (Med. Rec, Mar. 18, 1905). Hot-water and alcoholic lotions sometimes act promptly. In mild cases these are applied at night with very- hot water, either pure or combined with cologne water or camphorated alcohol. The water is gradually re- duced until pure camphorated alcohol or cologne water is used. Boric acid or borax may' be added to the lotions: 1 i)art to 50. Night and morning the skin should be bathed in very hot water (to re- duce the congestion), to which creolin, or a few drops of the following solu- tion, should be added : — 1} Corrosive sublimate .... 7K' grs. Tinct. of benzoin ....... 75 grs. Emulsion bitter almonds. 3675 grs. M. E. Lacour (Nord med., Aug. 15, 1900). Many of the less severe forms can be cured by prolonged bathing in hot water. The water should be soft, and the applications to the face should be made with a soft bathing sponge. The sponge, loaded with water as hot as can be borne, should be applied to the face. The bathing should last about five minutes, and should be done each night and morning; at the same time moderate pressure is applied to the sponge. After the sponging the face should be dried on a soft towel without rubbing, and bay rum should be applied freely. The face should not be touched by the hands until the time for repeat- ing the process. W. L. Hunt (Jour, of Med. and Sci., Sept., 1904). Have patient vigorously scrub his face, every night before retiring, with green soap and hot water. After rins- ing with cold water and drying the face, the following paste is to be applied : Betanaphthol, 5 parts; precipitated sulphur, 25 parts; green soap and lanolin, of each, 35 parts. Spread this over the involved rrea and allow it to remain fifteen minutes to one hour, after which it is wiped oflf. Length of application depends on the reaction produced; if left on too long, the skin reddens, or, after greatly prolonged contact, the epidermis desquamates. This paste acts probably by causing an inflammation of the skin, which e.xtends along the dilated follicles, thus inhibiting the secretion and pro- ducing shrinkage of the dilated seba- ceous glands. When the condition is improved, continue the applications at longer intervals to prevent recur- rence; also scrub face every second or third night. Burke (Penna. Med. Jour., March, 1911). Instead of camphorated alcohol there have been used with success : — Alcohol, 96°, saturated witli boric acid, and alcohol with salicylic acid, 1 to 30. The latter is strong and must be used witli care. Mercurial preparations have been variously extolled, but in late years have gradually given way to other more valual)le remedies. Mercurial lotions are efficacious in some cases, employed as follows : — R Corr. subl 1 part. Alcohol. 90° 100 parts. Dist. water or rose water . . . 150 parts. ACNE (STELWAGON). 255 At first this solution is weakened of the disease; especially useful when with one-half its quantity of water ; much seborrhea exists. In a few afterward, if no irritation has resulted, patients sulphur preparations cannot be the water is gradually reduced until the used, owing to the irritation caused, solution is employed pure. Sulphur may be employed in the fol- Other mercurial preparations, in lowing ways : — ointment form, such as the biniodide. Sulphur soap : with hot water, the the iodochloride, white precipitate, and suds being allowed to dry on to the mercurial plaster, viz. : — face. The ammoniated mercurial oint- Sulphur baths. ment, 5 grains, or 30 grains to 1 Sulphur lotions: hot water with 10 ounce, is highly recommended by to 60 drops for every one-half glassful Stopford Taylor. ^f liquid potassium polysulphide. Gordon Campbell recommends the An efifective method of using sulphur follovv-ing procedure:— . j^ the following:— The face is to be washed with water ^^ter washing with hot water and as hot as can be borne and some bland g^^p^ ^^^ following mixture is applied unirritating soap, and then, after care- ^^.jth a camel's hair brush :— fully drying the skin, the following lotion is applied once a day:— ^ Precipitated sulphur. Potassium bicarbonate, R Hydrargyri chloridi corrosivi. 12 grs. Glycerin Spiritus vini rectif 6 oz.— M. Laurel water. Effect for first few days will be to ^^''^'^ ^^^°'^ °f each 2 drs.-M. render condition worse; but, after this, T^g coating is left on during night- the lotion prevents perforation of the time and washed ofif in the morning pustules. with an emulsion of almond oil, and External drug treatment in both the skin is covered with oxide of zinc acne vulgaris and acne rosacea is usu- ,. ,, u -j. ^ ■ ^ ,, .. ^ . . c. 1 u • .u u . or bismuth subnitrate omtment pow- ally disr.ppoinling. Sulphur is the best ^ external preparation. Mechanical treat- ^^^^d over with fine starch, ment, such as the use of hot water, When the skin becomes irritated, the soap, massage, and the dermal curette, sulphur paste should be discontinued is exceedingly valuable. The opsonic ^^^^ ^j^^ ^-^^^ ointment applied alone method in acne vulgaris is promising. ., ,, • •, . , ,. , ■D ^ ^ ^ ^ t u ^\ A- until the irritation has disappeared. Roentgen treatment of both diseases ^^^ is the most valuable. In its certainty The following are useful: — of cure and frequencv of relapse it al- „ „ , , , . , ' -r rr., ^ , I> Sulphate of zinc, most approaches a specinc. 1 he tech- 0.7 ;• • ^ , , . , - . ^, V ■ ■ Sulpliuret of potassmm..ot each 1-4 drs. nique of using the X-rav, say, m acne, is ^„ , ^ . ^ ' jc ^u ■ ' ^ ^(^'' 4 oz. of paramount importance, it the ray is properly applied there should be few, ^ Precip sulphur if any, failures and no undesirable ef- ^^j^^^ " ; ^^ ^^^j^ 4 ^^^ fects. Cole CJour. Indiana State Med. ^j^^j^^j ^^ ^^^^^ 4 ^ ^^ Assoc, Mar., 1909). T^ 1JUJ1 ij-ii-ji R Precip. sulphur 2 drs. Formaldehyde, largelv diluted, has „ ' ' . •' . ." " Gum tragacanth, recently been tried with success. Camphor of each 20 grs. Sulphur preparations are by far the Ume water 2 fl. oz. most valuable in the external treatment Water . . ■ ■ to make 4 fl. oz. 256 ACNE (STELWAGON). Both these lotions are often made limate or cyanide of mercury. After more vakiable by the addition of 2 to these lotions the skin should be r ^ . r ^ • slightK- greased with lanolin, 10; 5 per cent, of resorcm. ^ ^ _, , ' ' i, , , . ,, , water, 20; and rose water, 5 parts. ^ Sulphur ointments are usually made ^he application of an aqueous solu- in the proportion of 1 in 10, with ben- tion of ichthyol, 5 to 10 per cent., is zoated lard, simple cerate, vaselin, also useful. Leredde (Bull. gen. de vaselin and lanolin, lanolin and sweet therap., 1903). almond oil or olive oil, or castor oil Salicylic acid acts well in from 1 to and cacao butter. 2>^ per cent, in various ointments. To the sulpluir may be added oxide Electrolysis has been recommended of zinc in equal parts; borax, 1 to 20; ^or the removal of the indurated salicylic acid, 1 to 50; naphthol, 1 to masses left on the skin. 10 or 1 to 20 ; resorcin or camphor, 1 In acne of tlie back the strong^est to 20 or 1 to 40. They may be per- applications, as a rule, are demanded, fumed with essence of rose, bergamot. Of especial value in some cases is the or balsam of Peru if desired. liquor calcis sulphuridis (Vleminckx's Sulphur soaps are sometimes more solution). This should be used at first convenient. diluted. The following- may be used :— Massag-e of the face is not to be Soap and precipitated sulphur, equal commended for acne, often doing dis- parts, tinct harm. Soap, precipitated sulphur, and lard, '^^'^ comedo is in the majority of equal parts. "^"^ '^\ forerunner of the acne . nodule and pustule. The comedo is Naphthol may be cautiously added ,,est removed by a comedo extractor, to the first of the series. which should have rounded edges. Among' other local treatments The pressure should be moderate, recommended are the application to ^"^ '^ *^^ comedo does not escape the pustules of carbolic acid, salicylic \\ '' ^"* !°, puncture with a narrow . . -^ bistoury. This should be done by the acid, or resorcin. An ointment of physician. The papules and pustules ichthyol, 1 to 4 or 1 to 8, is also useful. are treated by lancing. When more Tlie following resorcin paste is active methods are not employed, it recommended: ^^ °^ value to cover the parts with ■o „ . ^ , ,- mercurial plaster for a few nights. H Resorcin 2J/2-S parts. ,t . , , ., , , 7 „. . , /I- Various useful methods have been Zmc oxide, j • , , • , , ,. • f,^ , . , ^ devised, the mam local applications 'Starch of each 5 parts. ■ ^. r ^ u i- i- -j ,. ,. ,^v ,, consisting of sulphur, salicylic acid, I aseltn 12'/> parts. — M. . , A^, , '^- ^ resorcm, and soap. The best treat- This paste may remain on a day and ment, however, is the X-ray. In a night and then be removed with a "^^"y ^^^es irradiations will obviate piece of cotton. Cure is said to be *^^, "^"^f't^ ^^ lancing the nodules J ... ^1 s"d pustules. D. Lieberthal (Lancet- speedy, occurring in three or five days. (^Uj^j^,^ j^^^^, 3q j^q^^ It is a strong preparation, acting with -n e i ^ i • ^i i ^ ^ . . , , . Before undertaking the local treat- considerable energy in some cases. ^^^„^ ^^ ^^^^^ .^ .^ ;^^„ ^^ ^p^^ ^^^ In slight cases of acne of the face pustules, empty the comeoones and the following formula is recom- , _, mended: Eau de cologne, or 90 per sebaceous cysts, etc. These measures cent, alcohol, with resorcin or sali- often prove satisfactory in indurated cylic acid, 2 to 4 per cent., or sub- and rebellious acne. Some observers ACNE (STELWAGOX). 257 object, however, to the use of the curette. Facial acne gives favorable results under treatment by a glass vacuum electrode excited by the Oudin reso- nator and transmitting quite a strong current. The bulb should be rubbed over the skin without breaking the contact, and at the same time a con- stant stream of tiny violet sparks should pass from parts of the bulb not in the closest contact with the skin. The face should be somewhat red after an application lasting six or eight minutes during which the elec- trode is in constant motion. The writer is most strongly opposed to the practice of opening acne pustules. He has seen faces as badly marked as by small-pox. It seems much bet- ter to treat the case along the follow- ing lines: Rhubarb and soda inter- nally relieve any source of irritation, such as phimosis; cleanse the skm by vigorous washing with tar soap every night and then apply a soothing anti- septic salve, such as ung. zinci oxidi, 2 ounces (62 Gm.) ; pulv. acidi salicyl., 20 grains (1.3 Cm.). This treatment combined with that by high-frequency currents has enabled the author to permanently cure a number of cases of acne vulgaris and the disagree- able and intractable acne rosacea. Sinclair Tousey (Amer. Jour, of Der- mat.. Oct., 1911). Mild X-ray exposures of short dura- tion and low vacuum may often be advantageously employed, but should be done with great caution and as an aid rather than the sole measure of treatment. Its indiscriminate and in- judicious use is to be condemned. In the majority of cases repeated small doses of X-rays will bring about a satisfactory cure, even when all other treatments have completely failed. A third of a Sabouraud's pas- tille dose repeated at the end of a week, and then after fourteen days, is the system found to agree best in most cases. After this it is often desirable to keep up the effect of the 1- rays for a considerable time, at three weeks' to a month's interval, between applications. Sibley (Clinical Jour., Apr. 29, 1914). Repeated small doses of the X-rays not strong enough to induce appre- ciable reaction in the skin, or a single large dose with a reaction, seem to be able to modify the sebaceous glands to such an extent that the tendency to acne dies out. This proved true in a large number of cases. Its efhcacy is greater in acne spread over a larger surface, with numerous pustules, than in the less disfiguring, torpid type. Dos- seker (Therap. Monats., Aug., 1915). Dietetic measures are unnecessary. He removes all oil excess by pure alcohol cleansing of the face, the copious water drinking and X-ray 5 minutes to each side once a week, or if erythema occurs every other week. Le Fcvre (Ohio State Jour, of Med., Feb., 1917). The writer recommends the judici- ous use of the X-ray in acne. The nodular and keloidal varieties are not otherwise amenable to relief. Relapse after apparent cure by X-rays is rare. Should it arise it can be dealt with by further irradiation. Semon (Brit. Med. Jour., May 22, 1920). According to Bier, nature always meets a pathogenic substance with the same weapon, namely, hyperemia. This is shown either by scratching a sterile skin with a sterile needle or by infecting any organism with any irri- tating or poisonous germ, or, most commonly of all, by the reaction of the part when a small splinter is lodged in the skin. The object is to increase the local bloodrsupply. Bier's method has been tried in acne with some success. Bier's method for the treatment of acne consists in the appUcation of dry cups to the affected region for one-half hour once or twice a day. The sHCtion is slight, and the cup is removed and reapplied every one or two minutes. From two to five ap- -17 258 ACNE ROSACEA (STELWAGON). plications must be made over the same area l)efore improvement is effected. The method does not pre- vent the appearance of new pustules, though they become less frequent. Eight cases treated l)y tliis method alone produced marked improvement. Moschowitz (Med. Rcc, Jan. 13, 1906). Bier's suction cups found useful. Applied for repeated five-minute pe- riods with three-minute intervals, making two to five applications at each seance. Sibley (Lancet. Fcl). 4, 1911). Sir A. E. Wright's vaccine therapy has also been used with success in acne. As this investigator explains, no attempt is made to supply to the patient pro- tective substances produced in the organism of an animal vicariously in- ocvtlated, but the chemical machiner}- of the patient is induced to elaborate by its own efforts the protective secre- tion which is required for the destruc- tion of the pathogenic agent. Severe cases of acne often do bet- ter under vaccine treatment than comparatively mild ones; the most resistant to this treatment are usually those with abundant seborrhea, many comedones, and scanty foci of sup- puration. Vaccine treatment must be continued for 6 months at least, and long after all spots have ceased to appear, when diminishing doses at longer intervals will often prevent relapses and complete a cure. Sil)ley (Clinical Jour., Apr. 29, 1914). In Cornell University it was found that entering students showed 30.2 per cent, of the freshman class suf- fered from acne vulgaris; general in 17.8 per cent., and limited to the face in 12.2 per cent. Their treatment showed the superiority of well-known therapeutic measures over vaccine therapy. Indeed, T. J. Horder has well said: "The failures of vaccine therapy are probably more numerous than its successes." Fox (Jour. Amer. Med. Assoc, June 24, 1916). Henry W. Stelwagon, Philadelphia. ACNE BACTERIN. See Bac- TEKI.^L X'aCCINES. ACNE ROSACEA.— DEFI- NITION.— Acne rosacea is character- ized by a chronic congestion of the face, causing vascular dilatations ; and by changes in the cutaneous glands and tissues, giving rise to seborrhea, inflam- matory acne, and hypertrophic changes. SYMPTOMS.— The nose and malar eminences are especially prone to this disorder. It may also affect the fore- head, chin, the neighborhood of the ahe nasi, the cheeks, and less commonly the side of the neck. In women the chin is occasionally invaded. There are three forms of acne rosacea. The first is the erythematous and tclangiectasic. It may be characterized by temporary congestive spots on the face, showing themselves especially after meals and in the evening. These spots may be accompanied by no other lesion. This form is usually present in connection with more or less seborrhea, especially on the nose, which is gen- erally very oily. Again, the erythema- tous variety may be characterized by small vascular dilatations on the nose or malar eminences, which dilatations develop gradually, unite with one another, and form a network. This network is uniform in hue at a dis- tance, but nearby may be seen to be formed of congested surfaces over which are spread vascular dilatations. This degree of the erv^thematous form is almost always accompanied by sebor- rhea, enlarged nose, and dilated glan- dular orifices, especially in women toward the menopause and in wine- drinkers. The nose may be sliglitly violet Imed and be cold to the touch. ACNE ROSACEA (STELWAGON). 259 The second form is the erythematous acne, or true acne rosacea. In addition to the erythematous and congestive feature, there may be found in this variety a true acneic and acne-Hke ele- ment : papules, pustules and tubercles or nodules. In some cases the acne ap- pears before the congestion. There is a congestive red base with fine vascular dilatations and papulopustules of various sizes, often resting on an indurated violet-red base. In this variety there may also be in- crease in number and size of the vascular dilatations, increase in size and depth of the acneic indurations, and proliferation and hypertrophy of the derma. The third form is the hypertrophic acne, or rhiiiophyma. In this variety the glandular orifices are much en- larged, while the glands themselves may be ten to fifteen times increased in size. The tissues around them proliferate, forming a variety of pachyderma. The nose may be red or violet hued, covered with enlarged orifices, greatly increased in size, occasionally reaching consider- able dimensions (the so-called Pfund- nase of the Germans). Its exterior may be mammillated. (Brocq.) Two subdivisions of this form are rendered necessary by the difi'erencc in the pathology of each. The first, glandular, presents an embossed aspect, the hypertrophy being due especially to hypertrophy of the pilosebaceous glands ; the second, elephantiasic. pre- sents a smooth aspect, being due to chronic edema ; there are also vascular dilatations, with sclerosis of the derma. (Mdal and Leloir.) ETIOLOGY. — Women suffer more than men from the erythematotelangi- ectasic and acneic forms. Men only suf- fer from hypertrophic acne. It usually appears between 30 and 40 years, hi women, rosacea develops usually at from 30 to 45 years, and increases de- cidedly toward the menopause, after which it may recede. It may also, how- ever, develop at puberty. In young women and girls acne rosacea is frequently dvie to chlorosis, dysmenorrhea, or sterility. In some it recurs at each conception. Some authorities claim that, among the constitutional causes, heredity plays an important part. Cold feet, urethral and uterine dis- turbances, and constipation are also recorded as causes of the disease. Ex- ceptionally a factor in acne may be found in the mouth or teeth and be unilateral if the cause is one-sided (E. Besnier, Doyon). Dyspepsia, neuralgia, hemicrania, working with the head inclined forward, and disease of the nasal fossae are among the less frequent etiological factors (which afifect men more than women), while high heat, overheated rooms, high wind, sea air, cold, and cold water are occasional causes, espe- cially in men. The disease may become started in people who for several years have indulged in excessive hydrothera- peutic treatment. (Kaposi.) Certain occupations which expose to heat, cold, winds, etc., such as those of coachman, baker, smith, fireman, glass- blower, may also become primary causes of the trouble. Indiscretion in diet and alcoholic beverages are well- known factors. According to Kaposi, in wine-drinkers the nose is bright red, in beer-drinkers it is violet, while in spirit-drinkers it is soft, large, and dark blue. PATHOLOGY.— The vascular dila- tations of the face have been considered by some authorities as due to circula- 260 ACNE ROSACEA (STELWAGON). tory troubles caused by compression of the veins in the cranial foramina. A certain paretic condition of the vascular walls may often be looked upon as a cause. (Brocq.) The cutaneous nerves of the region affected have been found normal by E. Besnier. According to Leloir and Vidal, however, there is congestion of the deeper venous network of the skin ; dilatation of the same vessels and of the perifollicular vascular network, their walls being often diminished in thickness. There is also formation of new vessels. DIAGNOSIS.— Lupus Erythema- tosus. — The superficial, congestive variety shows a brighter and better defined redness; crusts or squamrc on the surface; sharper and more definite edges ; greater sensitiveness to pressure ; slight elevation above the surrounding surface. There are no papules, pustules, or tubercles. If any cicatrix be present, it is surely lupus erythematosus. Acne telangiectodes is an affection sui generis, and not identical with lupus follicularis disseniinatus; but it is iden- tical with the acnitis of P.arthelcmy, and must be distinguished from the disease known as folliculitis. It pre- sents no sort of etiological relationship to tuberculosis, and should be separated from the tuberculomata and the tuber- culides. It docs not take its origin in the sebaceous glands and, therefore, does not belong to acne. Pick (Archiv f. Dermat. u. Syphilis, Bd. Ixxii, H. 2, 1905). Circumscribed Congestive Sebor- rhea.— In this disorder there is a limited extent of patches, shallower and more uniform redness, with crusts covering them. Sycosis Coccogenica. — This is al- ways an inflammatory disease of the hair-follicles and perifollicular tissues. There are numerous papules and pus- tules, each i)erforated by a hair, and often capped by a small circular scale. The upper lip and chin are sites of predilection. The affection is usually painful. Congenital adenoma sebaceum also has a special location : the nasogenial furrow, the parts around the nose, mouth, and chin. It presents a mam- millated aspect, and its predilection for early youth and its normal evolu- tion serve to establish its identity. Eczema. — Erythematous, or pustu- iopaindar. eczema of the face may sometimes present diagnostic difficul- ties. In this disease, the more or less constant, and usually intense, itching, tlie serous or seropurulent secretion, and the desquamation will suffice to establish the diagnosis. Chilblains. — Changeableness of the lesions and ]>ains are peculiar to this disorder. Acneiform Syphilides. — Here the manner in which the elements are grouped, the long duration of their evolution, their tendency to ulceration, and consecutive cicatrix are important. Rhinoscleroma. — In this disorder there are hard or ivory-like masses im- l)eddcil in the nose. PROGNOSIS.— Acne rosacea docs not always increase; it may remain stationary or even recede, especially in women after the menopause. TREATMENT. — As to general treatment, it is especially necessary to pay strict attention to the good condi- tion of the stomach and intestines, by appropriate measures and suitable diet. Purgatives are absolutely neces- sary from time to time; laxatives should frequently be given and con- stipation should be avoided (Brocq). In many cases, especially where the hemoglobin percentage is low or the ACXE ROSACEA (STELWAGON). 261 bowels are sluggish and irregular, the use of Startin's mixture is effective, the formula for which is: R Magncsii sulphatis 30.0 Fcrri sulphatis 0.25 Acidi siilphiirici diluti .... 8.0 Sodii cliloridi 2.0 Infiisi gcntiaiuc q.s. ad 120.0 Directions : Take a tablespoon ful in half a gobletful of water one hour be- fore each meal, using a glass tube be- cause of the iron. If there is any indigestion this prescription may be al- ternated with the following : — B Papain 8.0 Sodium bicarbonate, Charcoal of each 16.0 Make into 50 tablets. Directions : Two tablets in a wineglassful of hot water before each meal. J. Philip Kanokj- (Amer. Jour, of Clin. Med., Aug., 1908). Proper circulation of lower limbs should be insured by adequate clothing. An}- abnormal condition of the genito- urinary tract or of the upper respiratory tract, especially the nose, should be cor- rected, while an}"thing tending to cause congestion of the face, such as tight collars or stays, should carefulh- be avoided. Sedentary- intellectual work, especially by gaslight, frequently ag- gravates these cases. On the supposition that a rheumatic diathesis is a possible etiological factor, various alkalies have been recom- mended, especially bicarbonate of soda or the various alkaline waters. Where the face is intermittently^ congested, quinine, ergotine, bella- donna, digitalis, and hamamelis have been suggested. These may be com- bined in a mixture, with or without the tincture of aconite-root. \'asocon- strictor drugs have but little influence. Perchloride of iron, tannin, ergot, and tincture of hamamelis are recom- mended by E. Besnier and A. Doyon. The following preparation is ex- tolled by Brocq : — IJ Quinine hydrobromidc, Ergotin of each 30 grs. Belladonna extract 6-12 grs. Lithium bcnzoate 30 grs. Excipient and glycerin ..... q. s. Misc. For forty pills. Sig. : Two before each of the two prin- cipal meals. Rhubarb or aloes may also be added if necessary. Study of 12 cases of acne rosacea by the fractional method of gastric analysis. In 5 there was complete achlorh3-dria throughout the period of the meal and in 2 an extreme degree of h3'pochlorh3-dria. Of the remain- ing 5 cases, 1 showed no secretion of free h3'drochloric until after 1 hour, and 2 showed a temporary high peak in the curve of acidit\-. w'ith an abrupt fall to the base line. There ' was also a tendency to rapid empty- ing, and a highlj- mucoid resting se- cretion, frequently of the viscid con- sistency of raw eggwhite. Dilute hydrochloric acid, 30 minims and up- ward, well diluted, after meals or during meals, yielded very satisfac- torjr results. Ryle and Barber (Lan- cet, Dec. 11, 1920). The local therapeutic agents are the same as in acne vulgaris ; though some irritable varieties of acne rosa- cea exist, it is usuall}^ necessar}- to act with greater energ}\ Hot water and mercurial prepara- tions are often of value. Mercurials are. however, much inferior to the sulphur preparations. The following- has been employed bv Bazin with success : — B Mercury biniodide 7^-15 grs. Lard 1 oz. — M. Sulphur preparations, as already stated, are, however, the most useful, those commonly employed in acne be- ing prescribed. In cases of average intensity derma- tologists frequently employ Vlem- inckx's solution, at first with 5 parts of water, then gradually making it 262 ACNE ROSACEA (STELWAGOX). strong-er until it is used pure. It cast off spontaneously. When there should be left on several minutes, and '^ much tension the surface may be r ,, , , i J. J. -J. covered with a clean rag that has followed by very not water; it may , ., • i , j -.u -iiri » -' -^ ' ■' been thickly spread with Wilsons often be left on overnight with advan- s^lve or some other suitable oint- tage. ment. In the presence of severe in- Green soap gives the best results in flammation an ice-bag maybe applied, obstinate acne rosacea, alone or when As a rule, frequent interruptions are , . . . .. 1 , unavoidable, and the treatment is used m conjunction with sulphur, . , n i ^ , ^ i ^ .1 •' therefore hkcly to last about three naphthol, or salicylic acid. It may be ^r four months. Zcissl (Miinch. med. used as in acne vulgaris or spread on Woch., Xu. 20, 1908). a piece of flannel ; the latter is then cut Surgical treatment in this disease is out to fit the afifected region, and left the most efficacious. (Brocq.) on as long as possible. It should not Electrolysis is another satisfactory be left on too long. When the irrita- method. A fine platinum needle is in- tion becomes too great, the application serted alongside of the vessel, and, if should cease and cooling prepara- possible, into it, and connected with the tions, such as the following, be used: negative pole, while the patient holds IJ Salicylic acid 7 grs. in his hand a cylinder in communica- Zinc oxide, tion with the positive pole. A large Bismuth subnifratc .. of each 30 grs eschar must be avoided. (Ilardaway.) Lycopodium K. dr. Electrolvsis of each dilated sebace- l aschn ^ drs. ^ ,,. / . , . , . j^^fifjlin 3 drs ^''■'^ follicle with a negative platinum T 1 ,, , , , , , rr needle and a current of from 4 to 6 lchth\ ol does not seem to be as em- , . „ . , , milliamperes is an enective, though cacious in acne rosacea as in some ,. ' _, ,,,11 ,, . ^. ^ ., , tedious, measure. 1 he needle should other varieties of acne, (brocti.) , , , • 1 r n- 1 • TT 1,11 r -7,/ be moved around in the follicle in or- Unna recommends daily doses ot //2 , , , , ... ^1 , . ^ ,, , , der to thoroughlv destrov it. grains of ichthyol internallv and lo- '^ " ',• -.Li • 1 ...1 1 J- 1 J • 4. In the carlv stages of acne hvper- tions with ichthvol dissolved in water, , • o- " , , r \ \ trophica, diet, a local spray of sulphur washing with ichthyol soap. Steam ^^^.^^^ .^,,^, electrolysis of the en- or sulphur-water douches have also larged sebaceous glands are sufficient, been used with good results. But when hypertrophy occurs, with A solution of iodine in glycerin, ap- deformity and tumors of the nose, ,. 1 ^ . , ., , . ^, J. surgical measures only are satisfac- plied twice dailv during three or four n-, .u r ^u ' ' r torv. The author prefers thermo- days, is recommended by Kaposi for cautery to the knife, and considers the more severe forms. l)Ut it is dis- grafting undesirable if this is used, figuring and not advisable for patients When it is, however, skin grafting outside of hospital wards. "^^y hasten recovery and prevent . scar contraction. Dubreuilh (Ann. de In a series of cases of acne rosacea ^^ i. 1 c i x^ inni\ , , . , „ Derm, et de Syph., Nov., 1903). the author succeeded in gradually re- moving the eruption by means of The ordinary galvanic or faradic painting with undiluted iron chloride, currents have been recommended by The applications were repeated every Cheadle and Pififard. morning and evening, and resulted in Scarification was formerlv a favorite a complete cure. A somewhat solid . . „, 1 ^ • ^ \ • \t- ^ ^' . ^ ^ r , ,, J , method. 1 he best instrument IS Vidal s crust is apt to form at the end or four or five days, and the paintings ordinary scarificator. The skin IS cut should be omitted until this crust is obliquely or perpendicularly to the ACOIN. ACONITE (SAJOUS). 263 vessels, then slightly obliquely across these so as to form lozenges, and as near together as possible (from 1 to 1^ mm. apart), and not deep enough to penetrate entirely through the der- mis, so as to avoid cicatrices. An hour afterward the part is washed with a corrosive sublimate solution, 1 : 1000 ; then in the evening or the fol- lowing day compresses dipped into an ammonium hydrochlorate solution, 1 : 100, or corrosive sublimate, 1 : 500, are applied. If too strong, warm water is to be added. If the reaction is too violent, starch poultices, bland poma- tums, or zinc oxide plasters can be employed. The treatment should be renewed in from five to eight days. Amelioration will occur in from eight to ten sessions, and marked improvement in from fifteen to twenty-five sessions. Scarifying should be begun in the lower part of the region to be oper- ated upon, in order not to be troubled by the blood covering the surface, ac- cording to E. Besnier and likewise A. Doyon. In the early stage of hypertrophic acne the scarification must be made deeper, and in many cases it is essential to also cauterize the glands deeply. In the advanced hypertrophic form direct removal with the knife is the best procedure. (Brocq.) Hypodermic injections of alcohol have recently been recommended. Phototherapy has likewise given sat- isfactory results ; both high-frequency current and the X-ray are of value in some cases. Henry W. Stelwagon, Philadelphia. ACNE VACCINE. See Bac- terial Vaccines. ACOIN, a synthetic compound used as local anesthetic, especially in dental and ophthalmic practice. It is designated as alkyloxyphenylguanidin and occurs as a white crystalline powder, readily solu- ble in pure cold water to the extent of 6 per cent., and in alcohol. A 1:200 aqueous solution injected under the skin causes a local anesthesia lasting about one hour. Acoin presents the draw- back, however, of being quite unstable, while producing greater irritation than cocaine, and is liable to produce necrosis. S. ACONITE. —The preparations of aconite usually employed are obtained from the root of the Aconitiim no pel I us (monkshood, wolfsbane), a conical tuber greatly resembling horse-radish. This resemblance has caused many deaths. Aconite-root is, however, brown in color, and when scraped does not emit the pungent odor peculiar to horse-radish. Again, instead of irri- tating the palate, as does horse-radish, aconite-root, when masticated, soon produces in the mouth a sense of warmth and tingling, soon followed by local numbness varying in duration ac- cording to the length of time the mucous membrane is exposed to the ef- fects of the drug. Aconite owes its activity mainly to the alkaloid aconitine, of which the dried root is officially re- quired to contain 0.5 per cent. PREPARATIONS AND DOSE.— Aconite in substance is not employed, and the preparations made with the leaves are no longer official. The tincture (tinctnra aconiti, 1916 U. S. P.) is no longer stronger than the English or French tinctures. It is a 10 per cent, tincture, i.e., it contains 10 Gm. of the drug in 100 c.c. Dose, 3 to 10 minims, every three hours. Its eft'ects should be closely watched, especially in anemic and corpulent indi- viduals and in those addicted to alcohol. 264 ACONITE (SAJOUS). The extract (extractum aconiti, U. S. P.), % to Ys grain, is also official, and likewise : The fluidextract {fluidextractum aco- niti, U. S. P.), /^ to 1 minim. The alkaloid aconitine (aconitina, U. S. P.), %()() gi'ain to V^oo grain (0.1 to 0.2 mg.), occurs in the form of col- orless tabular crystals slightly soluble in water, but soluble in alcohol, ether, and chloroform. Aconitine is a very active poison and causes the responsibility of the physi- cian to be involved to a greater degree than any other toxic. Its activity is markedly increased when it is adminis- tered hypodermically, and the injections are very j)ainful. These facts and the variations in strength of the various aconitines on the market have militated against its use, and it is best to utilize the other preparations, all of which owe their activity to aconitine. MODES OF ADMINISTRATION. — Internally aconite is usually better given in small and frequently repeated doses than in large doses at longer in- tervals. Thus the tincture may be given in 1 minim doses every hour until the desired effect has appeared or until distinct depression of the circulation indicates cessation of the drug. Aconite should be administered well diluted. In fever a dram of a mixture of 10 minims of the tincture in 4 ounces of water may be given every fifteen or twenty minutes. For the relief of pain, 5 minims may be administered as the first dose, smaller ones being then given at short intervals. For cardiac over- activity, doses of 2 to 5 minims (0.12 to 0.30 c.c.) may be given thrice daily. When aconite is used over a long period, a gradual increase in its action is observed. Even wdiere indicated, aconite should not be given freely with the intention of producing powerful effects, as its action in large doses is sometimes unexpectedly severe. Aconite may be administered inter- nally in granules, in tablets or tablet triturates such as are official in the N. F., or in solution in water (1 in 3200). Tison has used aconite nitrate dissolved in a mixture of distilled water, alcohol and glycerin, 1 minim of the solution containing %2oo grain of the salt. As stated above the alk- aloid should be employed with great caution, as individual intolerance of it has been repeatedly observed ; a third dose of ^30 grain (0.5 mg.) has been known to cause death (Lepine). Doses of Ksoo grain (0.1 mg.) may be given every two or three hours, the drug being stopped when the first signs of toxic action appear ; these are, accord- ing to Gubler: prickling of the tongue, a sensation of shrinkage in the face, and loss of elasticity of the muscular openings in this region. These are followed by general numbness and chilliness. A total amount of ^oo to %5 grain (0.66 to 1.0 mg.) in twenty- four hours may be considered the limit of safety. Dujardin-Beaumetz advised never to give aconitine unless its effects can be carefully watched. LOCAL USE.— Aconite is used locally in neuralgia and skin affections, the tincture sometimes diluted with alcohol, or the linimentum aconiti et chloroformi of the N. F. (fluidext. aconit. 4.5, chloroform 12.5, in alcohol 100), being applied. The alkaloid is also sometimes used in a 2 per cent, ointment or in the oleatum aconitinae, N. F. (2 per cent), but should never be applied to abraded areas. Undi- luted aconitine is absorbed through both mucous membranes and skin to a considerable extent. ACONITE (SAJOUS). 265 Subcutaneous injections of aconi- tine have been given for neuralgia, but the pain caused and the danger from prompt toxic effects are marked disadvantages. INCOMPATIBILITIES.— The al- kaloid aconitine in solution (1 to 3200 being saturated) is incompatible with tannic acid, gallic acid, mercurials, and Lugol's solution ; aconitine nitrate is precipitated as the alkaloid by alk- alies. Among the physiological in- compatibilities of aconite may be men- tioned digitalis, atropine, strychnine, strophanthus, ammonia and alcohol. CONTRAINDICATIONS. — By reason of its depressant action aco- nite is contraindicated in all cases in w^hich prostration exists or threatens. If the respiration is embarrassed ; if the heart is in asystole ; if the patient is depressed, recourse must be had to tonics and stimulants. In broncho- pneumonia, pneumonia after the pri- mary stage, typhoid fever, phthisis, valvular affections of the heart, and in all cases of collapse occurring in acute infectious diseases, aconite is particu- larly contraindicated. In no case where the heart is weakened or degenerated should the use of aconite be considered. Old age contraindicates its use to lower the blood-pressure in nephritis. PHYSIOLOGICAL ACTION.— Within half an hour after its adminis- tration, aconite commences to affect the general system, slowing and weak- ening the heart's action, lowering arte- rial tension, increasing the action of the skin and kidneys, and producing more or less muscular weakness in propor- tion to the amount taken. It causes a tingling sensation in the lips, extremi- ties, and, perhaps, the whole body ; it diminishes the rapidity and depth of the respiration, and causes disorders of vision, vertigo, and loss of tactile sensi- bility and sense of pain. The effects of a therapeutic dose last three or four hours. Aconite, when administered in suflfi- cient dose, is a powerful depressant of the sensory nerve ; some have believed that the stage of nerve paralysis is preceded by one of nerve stimulation, but Wood considers this doubtful. The. drug paralyzes first the sensor}- end- organs, next the nerve-trunks, and fmally the centers of sensation in the cord. The reflexes are correspondingly impaired. The power of voluntary movement, which continues after the cessation of the reflex functions, is finally lost, owing to the later action on the motor centers of the cord, and sub- sequently on the neiwe-trunks. The brain is practically unaffected by aconite. Laborde and Duquesnel state that aconite in therapeutic doses has a particular eft'ect in modifying special sensibility in the area of the trigeminal ; they believe this effect to be exerted on the bulbar receptive nuclei of the nerve. According to Cushny, the subjective sensory phenomena resulting from the use of aconitine are due to a marked primary stimulation and secondary de- pression of the sensory end-organs, tingling and warmth locally being fol- lowed by numbness when the drug is applied to the skin or taken by the mouth. According to Cash and Dunstan py- raconitine, obtained from aconitine by heating to separate a molecule of acetic acid, causes no tingling of the lips or tongue. It causes slowing of the heart, partly from vagus irritation, partly from depression in function of in- trinsic rhythmical and motor mechan- isms. After its administration activity 266 ACONITE (SAJOUS). of respiration is reduced (by central de- pression) to a degree incompatible with life. Neither muscular nor intramus- cular nervous tissue is strongly influ- enced by pyraconitine, but the spinal cord is impaired in its reflex function, and there is a curious condition of ex- aggerated motility. When aconite is applied directly to the heart, the number and force of the beats are lessened, and its action is finally arrested in diastole. It lowers the blood-pressure and pulse-rate when given internally by a direct depressant action on the heart itself, and also by stimulating the cardioinhil)itory center. Laborde found, however, that the con- tractility of the cardiac muscle-fiber itself was not directly modified by aconitine. Hare has called attention to the fact that the fall in pulse-rate from poisonous doses is sometimes preceded by a quickening due to a condition of weakness and abortive cardiac action. The stage of low pulse-rate is also fol- lowed by one in which the ])ulse is fre- quent and irregular. Upon the vaso- motor center aconite is believed by Cash and Dunstan to have a late depres- sant efifect. It also causes slowing of the respiration, with lengthening of the expiratory period, by depressing power- fully the respiratory center. According to some obsen^ers, small amounts of the drug produce, instead, stimulation of the respiratory function, while Cushny is of the opinion that aconitine has a primary exciting efifect on most of the medullar}^ centers — vagal, vaso- motor, respiratory — as well as the spinal motor centers. Aconite reduces the temperature both in health and in febrile conditions, probably through an action on the nervous heat-regulating mechanism. and by the circulatory depression it causes, it also increases the action of the skin, kidneys, and salivary glands. Increase of the gastrointestinal and biliary secretions is stated to have oc- curred. (Schroff, Rabuteau.) MODE OF ELIMINATION.— Aconite is excreted mainly by the uri- nary organs, though it has also been de- tected in small amounts in the saliva and the bile. ACONITE POISONING. — The symptoms following the ingestion of a poisonous dose usually show them- selves after a few minutes. The characteristic tingling, prickling, and subsequent numbness already mentioned rapidly extend from the mouth and fauces to the face, thence to the body and extremities. Great prostration and muscular impotency follow. Speaking requires marked effort. The skin be- comes cold and clammy, the perspira- tion covering the surface, and the tissues communicating to the hand an icy coldness. Muscular pains may be present in the early stages, especially in the face. There is often experienced marked epigastric pain with nausea and vomiting. Later on the nausea ceases, owing to paralysis of the stomach walls. The heart-beats are greatly reduced in number and power. The pulse is usually irregular, compressible, slow, and so weak, at times, as hardly to be palpable ; in the advanced stages, how- ever, it becomes abnonnally frequent. The breathing is labored, irregular, and shallow, the number of respirations being at first decreased, then increased. Cyanosis may appear. The tempera- ture is lowered, sometimes considerably. The pupils may become dilated or remain of normal size and react equally ; occasionally they are contracted. Ac- cording to Manquat, they undergo fre- ACOXITE (SAJOUS). 267 quent variations in size at first, then dilate. The eyes may protrude or be shrunken ; therefore they afford no dif- ferential information as to the nature of the drug used. The mind is usually clear, and the patient calm, though apprehensive of impending death. Disturbances of vision (diplopia, amblyopia) and of hearing (tinnitus, deafness), as well as vertigo, are frequently complained of. Occasionally epileptoid convulsions occur. Spasmodic purging, with rectal tenesmus and bloody stools, is occa- sionally present. Aconite causes paralysis of respira- tion and circulation, death being due to sudden arrest of the heart in diastole. Cases of criminal poisoning by aconite are rare, according to }\Iagill. In the Condon case, of Springfield. Mass., the defendant purchased a two- ounce bottle of tincture of aconite, one- half of which was placed in a pint bottle of port wine and sent to the per- son whose life was attempted, and who drank nearly one-half of the wine. The immediate efifect was dizziness, in- ability to move, and a peculiar creeping sensation in the muscles. The vision became obscure. Life was only saved by three hours of untiring efforts. Case of aconite poisoning in a woman aged 45 years, a multipara, who had suffered from rheumatism. shortness of breath, and swollen feet. She drank by mistake about 3 ounces of a liniment. At once she recognized her mistake and experi- enced a hot tingling in the mouth, then numbness, giddiness, gastric pains, and soon thereafter followed by collapse. A druggist gave ipeca- cuanha wine and a strong emetic. Sickness continued, and a violent at- tack of clonic convulsions super- vened. The medical man called in found the patient speechless, cold, pale. skin moist, pulseless, respirations very faint and irregular, and the pupils dilated and insensitive, but no ptosis. The temperature was 96.6° F. Terrible gastric and abdominal pains and violent irritation and prick- ling of the skin were succeeded by numbness. Three times after at- tacks of clonic convulsions she ap- peared dead, but when they ceased the mind was clear and unaffected. As a cardiac depressant, ipecacuanha had been given; a mustard emetic was now administered to save the en- feebled heart. The head was kept low, the feet v.-ere raised, a sinapism was placed over the heart, and hot bottles and flannels were applied to the lower extremities and abdomen. Strychnine and digitalis were given hypodermically, and brandy was in- ' jected per rectum. Artificial respira- tion was unceasingly kept up. After an anxious six hours the breathing became stronger, an irregular, inter- mitting pulse could be felt at the wrist, while the body warmth slowly returned. A little coffee and brandy were swallowed and retained. The crisis passed, and she recovered. The quantity of aconite taken may be roughh' estimated as suiificient to kill 6 persons. Inglis (Lancet, Jan. 21, 1911). Death occurs in from one-half to five and half hours, the average being, ac- cording to Reichert, three and one-third hours. The symptoms resulting frotn a poisonous dose of tlie alkaloid aconi- tine are the same as mentioned above, but they occur more rapidly ; hypoder- mically administered, aconitine may cause death in less than a minute. Treatment of Aconite Poisoning. — Death in these cases usually follows exertion by the patient. He should, therefore, be kept perfectly motionless in the recumbent position, even during emesis, his head btsing slightly turned and the dejections received on a towel. 268 ACONITE (SAJOUS). An important feature of the treatment is to keep the patient as warm as pos- sible ])}' means of warm blankets and hot-water bottles, taking- care not to place the latter against the skin. The head should also be kept warm. If the patient is seen early the stomach-tube should be used at once to empty the stomach. If no stomach-tube be at hand, apomorphine, V12 to % grain, should be administered hypodermically, or some other active emetic, such as zinc sulphate, 15 to 30 grains, be given by the mouth. Digitalis, sulphate of strychnine, and belladonna are the most effective rem- edies, but ether and ammonia sliould first be employed, owing to their great diffusibility. All these remedies should be used hypodermically, the stomach being unable to perform its functions. A dram of ether, ammonia, brandy, or whisky should at once be injected, and, after a few minutes, tincture of digi- talis, 15 minims; strychnine sulphate, y^o grain ; or tincture of belladonna, 10 minims, according to what the practi- tioner may have. Atropine has been recommended as the most powerful antagonist to the depressing effects of aconite on the circulation and respira- tion. The dosage should be regulated so as to reach the point of physiological action by frequently repeated doses. Nitrite of amyl may be given by in- halation, and warm, very strong cof- fee be injected into the rectum. Case illustrating the physiologic antagonism between aconite and bel- ladonna. The patient had taken by mistake hah' an ounce of a liniment composed of chloroform, aconite, and belladonna. This means 53.3 grains of aconite root, which represents % grain of aconitine, of which ^io grain has been known to be fatal. He also swallowed 40 ifiinims of fluidextract of belladonna ( L>. \\), which is equal to 0.3 grain of the total alkaloids. This would represent, approximately, thirty times the official dose of atro- pine. Of chloroform he took 40 minims, about eight times the official dose. The interest in the case lies in the fact that the lethal eflfect of a large dose of aconite was abolished by the simultaneous action of a large dose of belladonna. Muscular weak- ness, numbness of the extremities, and tendency to complete collapse were the only purely aconite symp- toiTis observed. Salivation, which is usuallj- present in aconite poisoning, was absent, and the usually con- tracted pupil was overcome by the action of the atropine. Finally, the intensely depressant action of aconite on the central nervous system was counteracted by the stimulating in- fluence of the belladonna. The ob- vious lesson to be drawn from the case is the great value which should be attaclied to hypodermic injections of atropine in aconite poisoning. Speirs (I'.rit. Mod. Jour., Aug. 15, 1908). Tannic acid is useful as an antidote. Wood recommends that it be followed by an emetic and cathartic to avoid the eft'ects of resolution of the poison by the digestive fluids. If the patient is seen when the stage of depression has begun through ab- sorption of the poison, the stomach- pump, gently used, is alone permis- sible, emetics at this stage being liable to cause arrest of the heart's action. Tincture of digitalis, in 20-miniiTi doses, should be injected hypodermi- cally and repeated as required, besides the other measures indicated. Fric- tions under cover, the rubbing- being directed over the heart, serve a useful purpose. Artificial respiration is of marked benefit and should be used per- sistently as long as any indication exists. Since the strength of the tincture has been decreased (U. S. P. 1905). the cases of poisoning have been greatly ACONITE (SAJOUS). 269 reduced, and are seldom in fact met with in literature. Hence the fact that practically all the instances recorded in these pages antedate the year of the last Pharmacopoeia. Series of cases, 6 of which were fatal, found in the literature of ten years : — Case 1. Tincture. 7 drams. Recov- er>^ Emetics ; morphine, 5^ grain ; fluid- extract of digitalis, 6 drops: strych- nine sulphate, ^ iijo grain ; brandy, 1 ounce; all hypodermically. Bj- the mouth, 2 gallons of warm water; fluid- extract of digitalis, 20 drops; coffee, 11 pints; whisky, 3 pints; extract of nux vomica, ^2 fluidram; port wine, ^ pint. P. F. Brick (Jour. Amer. Med. Assoc, vol. viii, p. 567, 1857). Case 2. About 8 drops of concen- trated fluidextract. Recover}'. Emet- ics, coffee, whisky (dessertspoonful). Heat Friction and sinapism. T. H. P. Baker (Amer. Pract. and Xews, vol. iv, N. S., p. 122, 1887). Case 3. Fleming's tincture, 1^ ounces. Recovery. Emetics, brandy, ether, digitalis, ammonia carbonate. Amyl nitrite and warmth. C. C. Brad- ley (N. Y. Med. Record, vol. xxxii, p. 155, 1887). Case 4. Tincture, Yi ounce. Recov- ery. Brandy by mouth and hj-poder- mically. Ether. One quart of cold, black coffee. Heat and posture. S. Barnett (X. Y. Med. Record, vol. xxxii, p. 761, 1887). Case 5. Amount not known. Pa- tient intoxicated at the time. Symp- toms of acute poisoning. Recovery. Emetics, brand}', ammonia, and digi- talis by the mouth. Sixty minims of tincture of digitalis hypodermically. Heat. Clara T. Dercum (Med. and Surg. Reporter, vol. Ixi, p. 1889). Case 6. Tincture, amount not known. Child, 16 months. Marked toxic symptoms. Recovery. Brand}' and fluidextract of digitalis frequently repeated in spite of vomiting. Byron F. Dawson (Med. and Surg. Reporter, vol. Ixii, p. 7, 1890). Case 7. Tincture, 2 drams. Death. Benjamin Edson (X. Y. Med. Record, vol. xxxviii, p. 365, 1890). Cases 8, 9, and 10. Dr. Edson men- tions certain other cases known of, but not treated by him, three of which died. The amounts taken in these were from 1 to 4 drams. Case 11. Tincture (B. P.), 1 ounce. Death in sixty-five minutes. Mus- tard, lavage, heat, ether, and brandy subcutaneously. L. M. Whannel (Brit. Med. Jour., vol. ii, p. 791, 1890). Case 12. Fleming's tincture, 1 dram. Recovery. Sulphate of zinc, tincture of digitalis, 20 minims hypodermic- ally. Whisky, 1 ounce, by the mouth, followed by calomel, 8 grains. L. M. Whannel (Brit. Med. Jour., vol. ii, p. 791, 1890). Case 13. Fleming's tincture, 1 tea- spoonful. Recovery. Mustard, spirit ^ of ammonia comp. (B. P.), tincture of belladonna, brandy. T. F. H. Smith (Brit. Med. Jour., vol. i, p. 1109, 1893). Case 14. Fluidextract, 4 drams. Recovery. Emetics, atropine, and brandy subcutaneously. Altenloh (X. Y. Med. Jour., vol. Ixvii, p. 358, 1893). Case 15. Tincture, 7^ drams. Re- cover}'. Mustard, digitalis, and brandy subcutaneously; digitalis, nux vomica, and brandy by rectum; ether and am- monia by inhalation; brandy and am- monia carbonate by mouth later. G. H. Tuttle (Boston Med. and Surg. Jour., vol. XXV, p. 678. 1891). Case 16. Mentioned by, but not seen by. Dr. Tuttle. Tincture, Sj^ drams. Death. G. H. Tuttle (Bos- ton Med. and Surg. Jour., vol. xxv, p. 678, 1891). Case 17. Preparation not noted. Four teaspoonfuls. Recovery. Sul- phate of copper, digitalis, wine by mouth; whisky by rectum; whisky, 5.^5 grain strychnine, and digitalin, %o grain, hypodermically. Warriner (X. Y. Med. Record, vol. xxxix, p. 521, 1891). Case 18. Tincture, 2 drams. Recov- ery. Apomorphine, stomach-tube, tincture of digitalis, 25 minims; aro- matic spirit of ammonia, 45 minims; brandy. Robinson (Boston Med. and Surg. Jour., p. 192, 1892). 270 ACONITE (SAJOUS). Reported by R. W. Greenleaf (Bos- ton Med. and Surg. Jour., July 15, 1897). [The tincture of aconite re- ferred to is that of the old U. S. P.— Ed.] Case of a man, aged 26, who drank about three-fourths of an ounce of the tincture of aconite. He imme- diately discovered his mistake, and took about a tablespoonful of ground mustard in water, but could not vomit. The writer administered cider vinegar al^out fifteen minutes after drinking the aconite. He drank about a half-pint and another half- pint out of a quart jar. In less than live minutes he was greatly relieved, and his pulse was much better. The vinegar almost immediately relieved the burning and choking sensation in his throat. His saliva, which was thick and stringy (hanging down three or four feet, at the writer's ar- rival, on his attempt to spit), did not change its character for at least half an hour. It gradually became nor- mal. All the symptoms gradually subsided. C. M. Swincle (Ilomeo. Recorder, Oct. 15, 1908). THERAPEUTICS.— Aconite is mainly used as a circulatory sedative. It lessens the blood-pressure by dimin- ishing the force and rapidity of the heart's action, and is. therefore, indi- cated where a frequent and tense pulse is associated with excessive cardiac activity. It also tends to counteract spasm and relieve itndue excitability of the nerve-centers, though its prop- erty of depressing the cutaneous sensory nerve-terminals is more marked, and is frequently availed of in neuralgic affections. In some patients, and under some conditions of acute infection, like that of acute bronchitis, the reaction of the systein is almost violent. The temperature of the patient rises rapidly to 104° F. (40° C.) or higher, the heart l)eats with greatly increased vigor and frequency, there is a full pulse of high tension, a considerable rise in blood-pressure, and an accel- eration of respiratory activity. So sharp is the attack of the invading organism, and so vigorous the reac- tion of the system, that for the time being there seems actual danger of nature overstepping herself and cre- ating mischief through excessive activity. It is in such cases that some external regulating influence seems advisable. In such reactions aconite is the only drug whose pharmaco- logical provings show a true indica- tion. A. D. Bush (N. Y. Med. Jour., Jan. 22, 1916). Aconite causing increased respira- tion, it is indicated where, Avith a high pulse, there is dryness of the skin. The evaporation of sweat from the surface and the heat radiation due to the increased peripheral circti- lation resulting from relaxation of the cutaneous capillaries also cause a reduction of temperature. Aconite also possesses diuretic properties. Hence it appears to be endowed with all the qualities requisite in the in- cipient stage of uncomplicated in- flammatory disorders, as an anodyne sedative. Aconite is the most efficacious vasodilator when given systematically in full doses. Aconite thus adminis- tered at once reduces l)lood-pressure, produces a full and compressible pulse, and greatly increases the per- centage of the elimination of urea in interstitial nephritis. He prefers it to all nitrites, as their vasodilating effects are too transient, the most prolonged of them, that of the ery- throl tetranitrate, lasting for less than an hour, which is by no means sufficient for such a permanent mor- bid condition of general arterial con- traction, with heightened blood- pressure, as is present in chronic in- terstitial nephritis. The most im- portant action in interstitial nephritis is to increase the elimination of urea. W. Hanna Thomson (Amer. Jour. Med. Sci., Jan., 1915). ACONITE CSAJOUS). 271 In children aconite may be given whenever the spasmodic element is clearly marked : in fever preceding at- tacks of quinsy, pharyngitis, etc. ; in asthma and the asthmatic crises of bronchial adenopathy ; in pertussis and other spasmodic coughs; in laryngismus stridulus; in palpitations associated or not with hypertrophy of the heart, and in convulsions. The physiological effects enumerated afford sufficient ground for its value in the reduction of all the phenomena at- tending the fever: high temperature, dry skin, hard and frequent pulse, etc. The tincture is preferable here, as it is in all other disorders. The best effects are produced by means of small doses. One minim is first given, then another minim in one-half hour. After that, 1^ minims are given every half -hour until the febrile symptoms are reduced or until physiological symptoms of the drug appear. Aconite should always be greatly diluted. Its antipyretic power being less than that of certain newer remedies (coal- tar antipyretics), however, the latter generally (though very much less than formerly) find more favor where a marked reduction of temperature is desired, unless the additional indica- tions for the use of aconite, such as an overactive heart, frequent pvilse, or dry skin, be strongly marked. Its action in favoring perspiration may be enhanced by combination with other diaphoretics, such as the alkalies or pilocarpine. Aconite is used in the fever attend- ing the incipient stage of catarrhal disorders. It may be used as an anti- pyretic in continued fevers and in- fectious diseases, — variola, scarlatina, erysipelas, etc.. — l)ut large doses are usually required, involving corre- spondingly great danger. It is better used in moderate doses for general sedative and diaphoretic effects in less severe infectious fevers, such as measles, mild scarlatina, rubella, and in the group of "ephemeral" fevers. According to Tison, aconitine re- duces the pain and shortens the duration of erysipelas; he used acon- itine nitrate in doses of %4o grain every two hours, not exceeding 10 such doses daily. In the reflex fever which some- times follows the use of the catheter it has been found very efficient by several observers. In acute disorders of the nose, throat, and lungs the sedative effects exerted by, aconite upon respiration through its influence upon the respiratory center are added to the properties previously enumerated. Hence its use in acute coryza, pharyngitis, tonsillitis, trach- eitis, bronchitis, pleurisy, and pneu- monia. Dujardin-Beaumetz uses aconi- tine w^hen the lungs are congested, and especially in influenza. In all of these, 2 drops of the tincture every hour should be administered until the physiological effects — ting- ling and numbness of the lips and tongue — are experienced, when the remedy should be given less fre- quently. After the initial stage of the aft'ections enumerated, aconite should be discontinued, especiall}- in pneu- monia, in which affection its adminis- tration is positively harmful as soon as the asthenic stage begins. Aconite has been used in hemoptysis and epi- staxis to lower the blood-pressure and favor cessation of the hemorrhage. In the chronic disorders of the respira- tory passages — inclvtding phthisis — it is more hurtful than therapeutically beneficial. In children aconite has proven useful in ACONITE (3AJOUS). in coryza, tonsillitis, spasmodic croup, asthma, whooping-cough, etc. Aconite has been employed in all forms of rheumatism, as well as in gout, to relieve pain and reduce con- gestion. It is especially indicated when the skin is dry. It is believed to have particular value in the acute rheumatic pains due to exposure. In chronic rheumatism it may be used in the form of a 2 per cent, ointment of aconitine. Hutchinson has found tincture of aconite l)eneficial in rheu- matic iritis. He gives 5 minims three times a day, in conjunction with potassium iodide and the alkalies. Meningitis, pericarditis, and peri- tonitis are mentioned concurrently owing to the fact that their early manifestations are equally influenced by aconite. In peritonitis especially, its effect as an anodyne tends to pre- vent vomiting: an important feature. In pericarditis it increases the chances of recovery by reducing the number of pulsations, thus prolong- ing the resting periods between beats. It should, however, be used with caution in these conditions, in view of its somewhat variable general depressant action. The sedative effect of aconite upon the sensory nerves and nerve-endings has led to its frequent use, internally or locally, in neuralgia and neuritis. Certain authors consider it specially effective in neuralgia of the trifacial nerve. In neuralgia of the intenuittent type, a combination of aconite with quinine will often be found serviceable. In the form of neuralgia characterized by exacerbations during damp weather aconite is sometimes efifective in small doses frequently repeated. If the pain- ful spot does not cover much surface, application of the tincture over it with a camel's hair pencil contributes mark- edly to hasten the relief. The drug may also be applied as a liniment or by inunction (see Modes of Administra- tion). The pain of neuritis resulting from exposure to cold is sometimes favorably influenced by aconite. In pain due to disturbances of the central nervous structures, however, the drug has not been found of great value. By lowering arterial tension and diminishing the number of heart-beats it may be of marked advantage in func- tional cardiac disorders, but when organic lesions are present it had better not be used. It is not infrequently employed in uncomj^licatcd hyper- trophy, in nervous palpitation, and in the tobacco-heart, to antagonize ex- aggerated action, but its effects should be closely watched lest incip- ient degeneration be present. The dose generally used is from 2 to 5 minims of the tincture three times daily, though some advise larger amounts. A 2 per cent, ointment of the alkaloid aconitine has sometimes been applied to relieve pain and itching in affections such as herpes zoster, eczema, pruri- tus, etc. As suggested by Dr. G. W. Rob- erts, a solution of aconite in water is very efticient in stubborn pruritus. One dram (4 Gm.) of the tincture in 8 ounces (250 Gm.) of water or twice this strength may be used to "bathe" the itching area, using a soft cloth or sponge. H. T. Webster (Elling- wood's Therapeutist, Sept. 15, 1909). Dysmenorrhea due to congestion of the pelvic organs, metrorrhagia, and amenorrhea resulting from ex- posure to cold have all been mark- edly benefited by aconite. In the vomiting of pregnancy aconite in moderately large doses is often found ACROMEGALY (LAUXOIS AND CESBRON). Z/o to give relief, owing to its sedative effect upon the nervous structures involved in the reflex act. Aconite has been used with benefit in acute gonorrhea, 1 minim of the tinc- ture being given every hour (Ringer). It is also advantageous as an anodyne in epididymitis. C. E. DE M. Sajous, AND L. T. DE M. Sajous, Philadelphia. ACROCYANOSIS. See A ascu- LAR System, Disorders of, under Acroparesthesia. ACROMEGALY: PIERRE MARIE'S DISEASE.— DEFI- NITION.— Acromegaly is a general syndrome due, in almost every instance, to tumor of the hypophysis, character- ized by progressive enlargement of the osseous and other supporting tissues, and primarily and chiefly noticeable in the extremities. It was first described by Pierre ]Marie in 1886. SYMPTOMATOLOGY.— The most prominent characteristic of the "acro- megalic dystrophy is, as stated above, a progressive enlargement of the extremities. Although the de- formities are particularly noticeable in naturally prominent portions of the body, they also involve other regions, such as the skull, face, spinal column, and thorax, and are ven,- marked in these regions as well. An outline of the general appearance of the acromegalic patient — that odd, ungainly, and unharmonious creature — may prove profitable before the disease is studied in detail. His enormous, clumsy hands seem all the more massive from the fact that the forearms have retained their normal proportions. They present a "stuffed" appearance, and ter- minate in thickened, sausage-like fin- gers. His broadened feet are mere paws, with toes of exaggerated size. The face is long, the forehead narrow and retreating, and the supraorbital arches enlarged; the eyes often project forw^ard from between the thickened eyelids ; the nose stretches out laterally its fleshy alae; the lips are enormous, especially the lower, wdiich is everted; the lower jaw is strongly prognathic; the tongue, unusually large, frequently protrudes from the mouth. This repul- sive and beast-like head, bounded later- ally by ears of monumental size, is bent forw^ard and set deeply between the shoulders. Though of average stature, or above the average, the subject ap- pears partially collapsed; the curvature of his back and the thoracic deformity contribute to his humiliation, which is further accentuated by his torpid and melancholy demeanor. From a distance his appearance is so striking that the diagnosis can be made without detailed inspection. W'hen the deformities are fully developed, all acromegalics bear a strong resemblance, and the adage, "ab nno disce omnes," is here truly appli- cable. The increased bulk of the hands is often the first change to attract atten- tion. The hands become broader and thicker without augmenting in length. The hypertrophy involves all the com- ponent tissues of the part, — bones, mus- cles, subcutaneous cellular and fatty tis- sues, and skin. The latter is hard, firm, free of edema, and somewhat darkened in color. The interphalangeal folds, ab- normally developed, extend betw^een what may be called wads of flesh, — -the "main capitonnee." The thenar and hypothenar eminences are greatly over- developed, and the linear grooves of the palm are transformed into deep gutters. 274 ACROMEGALY (LAUXOIS AND CESBRON). The fingers are somewhat flattened from before backward, and are of equal thickness distally and proximally. The thumb measures up to 12 cm. in circum- ference (Lombroso), the index finger 9 cm., and the medius 10 cm. The nails remain relatively small. They become flattened, turn up at the edges, and show longitudinal striations. In exceptional cases a club-shaped deformity of the fingers, or the presence of nodosities at the interphalangeal joints, has been noted. Notwithstanding the unusual proportions of the acromegalic hand, its functions are generally preserved, complete flexion becoming impossible, however, in cases where the palm is markedly thickened. De Souza-Leite observed the "dead finger" phenomenon twice in 38 cases. In contradistinction to this massive voluminous, or "transverse" type, Pierre Marie has described a second variety of deformity involving the hands. In this type they again undergo a general in- crease in size, but there is added a growth in length which is about propor- tionate to that in breadth. Being longer, the hands thus appear lighter and less clumsy than in the massive form, where the overgrowth is almost solely trans- verse. This "longitiidinar' type is seen more particularly in subjects in whom the dystrophy developed at a relatively early period. We have met with it in our infantile acromegalic giants. These deformities of the hand gen- erally stop at the wrist, at least during the earlier stages. Later on, the hyper- trophy becomes generalized, the other segments of the upper extremity — fore- arm and arm — being also involved. The feet, like the hands, become broader and thicker, without greatly in- creasing in length. They present the same fleshy pads, surrounded by deep grooves. The skin is darker, but is of similar consistency. The toes, especially the great toe. reach altogether remark- able dimensions, and the nails are af- fected much as in the upper extremity. According to A^erstraeten, the heels are always enlarged. The hypertrophic en- largement generally terminates above the leg. The knee, if early involved, is enlarged but slightly, and the foot al- ways contrasts, by its exaggerated bulk, with the rest of the limb. The acromegalic fades, besides the characteristics already noted, includes a striking prominence of the supraorbital ridges, which project to an extent cor- responding to the degree of enlarge- ment of the frontal sinuses. The eyes are lacking in expression, and appear relatively small in comparison with the capaciousness of the orbits, notwith- standing the exophthalmos occasionally observed. The eyelids are thickened either /» toto or merely in the region of the tarsal cartilages. The temporal fos- sae becoming deeper, the malar promi- nences appear to stand out more strongly. The nose undergoes general enlargement, and is distinctly broadened and flattened. Its alse are heaviest inferiorly, and the septum is doubled in thickness. The lips are enlarged, particularly the lower, which is also everted. The mouth, often half open, reveals a tongue of enormous bulk. The movements of the tongue are poorly ex- ecuted; the organ interferes with mas- tication and articulation, is frequently injured by the teeth, and sometimes shows fissures at its borders. The roof of the mouth, soft palate, faucial pillars, tonsils, uvula, and larynx all exhibit hypertrophic changes. In female sub- jects, the thyroid cartilage, in its hyper- trophied state, recalls the "Adam's apple" normally seen in the male. Acromegaly. (P. E. Launols.) Acromegalic Profile. (P. E. Launois.) ACROMEGALY (LAUXOIS AXD CESBRON). 275 Laryngoscopic examination reveals both elongation and thickening of the vocal cords. These various changes in the organ of phonation impart to the voice a distinctive deep and at the same time metallic quality. While the alterations in the superior maxilla are apparently not pronounced, those involving the lower jaw are some- times extremely marked. The chin, large and massive, projects downward and forward, forming an obtuse angle with the rami of the jaw-bone. The lower teeth, which Henrot has found to be hypertrophied, are spread apart, and, owing to their forward projection, can no longer be opposed to the upper dental arch. The profile is most characteristic, and bears witness to the extraordinary de- gree of prognathism sometimes at- tained. The description of the acro- megalic facies would not be complete without a mention of the broadened ears, with their lobules of undue size. The facial skin is dry, brownish yel- low in color, and often presents warty excrescences. The hairs covering the head are individually thickened, and, taken collectively, apparently exhibit a heavier growth. The eyelashes and other short hairy appendages are also coarse and stiff. The bones of the cranium proper show modifications similar to those in the facial bones. These changes will be described later, when the results ob- tained by radiogr?/phic examination are discussed. In the spinal region, the vertebras, taken as a whole, show increased vol- ume. As a result, changes in the spinal curves are brought about, consisting. more specifically, of a cervicodorsal kyphosis, with or without lumbar lor- dosis and scoliosis. The thorax becomes more capacious and undergoes alterations in shape. It becomes prominent anteriorly. Though its anteroposterior diameter is increased, it is flattened laterally. The broadened sternum tends especially to spread out above, and develops transverse ridges. The clavicles become thickened and their curves exaggerated. The ribs come mutually into contact, or even overlap, and the costal cartilages become ossified. The lower costal arches slant Acromegfalic macrogrlossia, (P. E, Launois) downward, sometimes so markedly as to reach the crest of the ilium when the subject is in the sitting posture. The scapulae are thickened, and their acro- mial and coracoid processes stand out in bold relief beneath the skin. These deformities interfere in some degree with the thoracic excursions, sufficiently so, indeed, to bring about, among acromegalic subjects, a modifi- cation in the type of breathing, which becomes permanently abdominal. \Mien they are all present in the same patient and are very pronounced, a double hump in the back may be pronounced, recall- ing the classic conformation of the Ital- 276 ACROMEGALY (LAUNOIS AX 13 CESBROX). ian Punchinello, whom Pierre Marie considers the ancestor of acromegalics. The dystrophy makes its first appear- ance at the distal ends of the extremi- ties. The patient's attention is often attracted to the condition by the con- stantly increasing tightness of his gloves and footwear. In some instances the Cervicodorsal kyphosis in a case oi acromegaly. (I'ierre Marie.) family or neighbors notice changes tak- ing place in the facies. Once estab- lished, the affection progresses steadily and more or less rapidly. If the patient be a woman, she becomes aware of the progressively larger size of thimble she requires in her sewing. The male pa- tient, on the other hand, is struck by the increasing diameter of his headgear. From the distal portions, the changes proceed to the proximal segments of the limbs, which, by their hypertrophy, may assume a markedly athletic aspect. Muscular power, however, almost al- ways shows a gradual decrease ; not- withstanding their bulk, the contractile power of the muscles does not bear the normal ratio to their size. A certain degree of muscular atrophy has occa- sionally been noted ; in a case studied by Duchesneau (These de Lyon, 1901) it was so pronounced as to lead this observer to suggest the advisability of differentiating an amyotrophic form of the disease. The muscles show no note- worthv electrical disturbances: their ex- citability is diminished according toErb, exaggerated according to A^erstraeten. The patellar reflexes are either normal, diminished, or lost; they are never ex- aggerated. In certain joints, such as the knee, wrist, and elbow, there have been ob- served enlargement and painful crack- ling, recalling somewhat the phenom- ena noted in mild arthropathies. The circulatory system presents an interesting group of alterations. \'ari- cose veins are said to be frequent, and the heart is often hypertrophied. [hi 1895 Huchard pointed out the existence of more or less marked cardiovascular dis- turbances. His pupil, J. B. Fournier (These de Paris, 1896), having collected 25 cases, including 12 with autopsy, was led to distin- guish two varieties of cardiac hypertrophy, the one, slight and without degeneration of the muscular fibers; the other, accompanied by sclerosis and atrophy of the contractile elements. Launois and Cesbron.] Symptomatically these changes in the cardiac tissues find their expression in palpitations, arrhythmia, and dyspnea, and may result finally in asystole. Syn- copal attacks are said to be not imcom- mon. Spinal deformities, when marked, may result in dilatation of the right heart. Acromegaly in the Aged— Strabismus. (P. E. Laimois.) ACROMEGALY (LAUNOIS AND CESBRON). 277 H}^pertrophy of the lymphatic vessels and glands has also been reported. Seusatioi, on the whole, does not ap- pear to be affected. Unusual sensitive- ness to cold is, however, present to a certain extent. The various deformities that we have described arise and progress, as a rule, without giving rise to pain. In some instances, however, their develop- ment is accompanied by more or less severe painful crises, sometimes re- ferred to the viscera, at other times to the limbs. While sometimes taking the form of a simple myalgia, they may also striking component of the syndrome re- sulting from tumors of the hypophysis, and it is because it has drawn our atten- tion to the hypophysis that the syn- drome due to hypophyseal growths has brought forth such a wealth of litera- ture as to make it at present, perhaps, the most abundantly discussed of the syndrome caused by brain tumors. We consider acromegaly to be an in- tegral part of the hypophyseal syn- drome, and, indeed, with the exception of certain rare cases acromegaly unac- companied by tumor of the hypophysis does not occur, while, on the other hand, Series of thimbles used by an acromegalic woman. develop into severe neuralgia, and are then aggravated by exposure to cold and dampness. This painful form of the disease (Sainton and State, Revue Neurologique, p. 30, 1900. and These de Paris, 1900) may also assume the rheu- matoid type when it becomes localized in a certain group of joints. THE HYPOPHYSEAL SYN- DROME.— Until recent years the nat- ural history of acromegaly would have been covered by a description such as the above. The advances since made, however, both along clinical lines and in the pathology of the disease, owing to the use of the X-rays and to im- proved histological technique, have brought about modifications of our ear- lier ideas. Previously considered an in- dividual affection, to which the name "Pierre Marie's disease" had properly been applied, acromegaly was found to be, in reality, only the most peculiar and the close relationship of the disease to such tumors seems established. The affection generally makes its ap- pearance long before the other compo- nents of the syndrome, which may be interpreted as disturbances due to com- pression ; on the other hand, in no case has a tumor in the region of the hypophysis been known to produce acromegaly unless developed from the hypophysis itself. Acromegaly almost certainly implies the existence of a tumor of the hypophysis. The converse is, however, not always true, every tumor of the hypophysis not necessarily resulting in acromegaly. Clinically, tumors of the pituitary, the frequency, nature and characteristics of which we shall mention later, betray their presence by an aggregate of signs and symptoms included under the term "hypophyseal syndrome." We may divide these signs and symptoms, fol- 278 ACROMEGALY (LAUXOIS AND CESBRON). lowing the example of the obstetricians, into the three following groups: 1. Probable signs and symptoms of pitui- tary tumor. 2. Quasi-positive signs and symptoms. 3. Positive signs. The first are those of brain-tumor with special localization. Through its increased size, the pituitary expands the bony fossa in which it is lodged and soon begins to project upward above it, indenting the lower surface of the cere- brum. It exerts more or less pressure on the neighboring structures, and causes a certain degree of increased in- tracranial tension. The earliest symptom of it is head- ache. The pain tends to become local- ized anteriorly ; these patients often complain of a sensation of heaviness "which impels them half unconsciously to rub their forehead and eyes, as one does ordinarily upon awakening" (Rayer). In certain cases, the ])ain is more definitely localized. In some cases the progress of the disease is so nearly painless that the discovery post mortem of an almost complete flattening of the basal convolu- tions, whereas in life only trifling mi- graine had l)een recorded, becomes a matter of surprise. Along with the headache should be mentioned vertigo and vomiting of cere- bral type, which are among the usual signs of intracranial tumors. With the symptoms are generally as- sociated melancholic tendencies, loss of memory, and mental and physical tor- por. Apathy sometimes reaches such a degree that the power of executing voluntary acts seems practically lost. It was very pronounced in the peculiar case described by Rayer: "During the morning visit, when asked to rise, he promised to put on his clothes at once, yet at 5 o'clock in the afternoon, not- withstanding repeated requests by the nurse, he was still in bed. When obliged to relinquish his room in the daytime, he would leave only to sit motionless in an armchair or to slumber in an ad- joining room. The positions he assumed were those of an exhausted, flaccid, and semiunconscious individual." Convul- sive movements may also be observed, sometimes confined to the face, in other instances involving the limbs. In establishing a diagnosis of brain tumor in general, and of tumor of the hypo])hysis in particular, no signs should be overlooked, and we must, therefore, not forget to mention as possible symp- toms cramps, contractures. These may be related to the coexisting hydro- cephalic condition, since they disap- I)eared, in a patient of von Hippel, upon the removal of cerebrospinal fluid through a nasal opening. The tremor observed by Stroebe and the ataxia of the lower extremities reported by Hen- neberg are probably to be referred to some similar cause. Peculiar anomalies of taste occasion- ally appear, consisting of strongly ex- pressed desires on the part of some pa- tients to eat most unusual articles of food. Tinnitus aurium, peculiar in that it appears only on the side upon which the patient is lying, has been noted. Pressure may be exerted upon the sinuses adjoining the hypophysis and cause disturbances in the venous circu- lation, as shown by facial edema. The writer, on the basis of 4 cases observed by him, emphasizes the im- portance of acromegaly of the larynx, the laryngeal changes being sufficient to produce stenosis demanding tra- cheotomy. In one instance the lat- ter operation alone saved the pa- tient's life; in another case marked changes in the larvnx ended in sud- ACROMEGALY (LAUNOIS AND CESBRON). 2/9 den death apparently from asphyxia. In 3 of the 4 cases the laryngeal image was not symmetrical although the laryngeal enlargement seemed so on palpation. Asthma-like attacks or dyspnea or a harsh and weak, or masculine voice in the female, may form part of the sj^ndrome. Chevalier for weeks at a time between 34° and 36° C. (931/5° and 96y5° F.) without the supervention of any sign of collapse. Torpor and asthenia are, as we have stated, among the ordinary manifesta- tions of acromegaly. Exaggeration of these symptoms, in the hypophyseal Young acromegalic woman. In lower rig-ht-hand corner, same patient at the age of 20 soon after onset of tlie affection. (P. E. Launois.) Jackson (Jour. Nov. 30, 1918). Amer. Med. Assoc, Among the circulatory changes that may be produced is to be added to those already mentioned the somewhat para- doxical acceleration of the pulse, re- ported by Engel. A no less singular manifestation is lowering of the internal temperature, which, in a patient of Bartels, remained syndrome, may give the appearance of "sleeping spells." True psychoses occur with extraordi- nary frequency in cases of tumor of the hypophysis. Schuster, who has made a special study of the psychic dis- turbances observed in brain tumors, be- lieves that they are met with in almost one-half of the cases of tumor of the hypophysis. This proportion will not 280 ACROMEGALY (LAUNOIS AND CESBRON). seem surprising if we recall the fact that the first pathological observations on hypophyseal tumors were made in asy- lums for the insane. History affords a conspicuous example of this in the person of Cromwell's giant porter, a maniac with prophesying tendencies, whom it was found necessary to confine. In the literature on the pathology of tumors of the hypophysis we often come across the words "amaurotic insanity" as a heading in clinical records. This accompaniment of these tumors, long overlooked, was but recently given due emphasis by Frohlich, and particularly by Cestan and Halberstadt. The vari- ous forms of delirium, delusions of per- secution, myster}^, and the manic-de- pressive psychosis may be encountered. An interesting fact has been reported by Moutier (" Acromegalic : crises epilepti formes avec equivalents psy- chiques," Revue neurologique, Nov. 8, 1906) in the occurrence in an amblyopic acromegalic of rather frequent epilepti- form seizures, due evidently to the cerebral tumor present. In the inter- vals between seizures he was subject to "absent periods," during which he would sometimes remain perfectly still, or else perfonu a large number of unreasoning acts of which he lost all memory after the attack had subsided. Polyuria and glycosuria are often en- countered in cases of tumor of the hy- pophysis. That the presence of sugar was not more frequently reported by the earlier observers is due to the fact that they were not in the habit of ex- amining the urine in their cases system- atically. Loeb (Deutsch. Archiv f. klin. Med., p. 449, xxxiv, 1884; Cen- tralbl. f. innere Med., 1898) was the first to point out the frequency of melituria in disease of the hypophysis. He explained it as being due to the pressure which may indirectly be ex- erted by tumors of this gland on the floor of the fourth ventricle and neigh- boring structures. Glycosuria of hypophyseal causation, though more or less constantly present, may show wide variiations in intensity. In a patient of Finzi (Boll, della Soc. Med. di Bologna, No. 4, 1894), for in- stance, the sugar, after having been present in large amounts, gradually dis- appeared completely from the urine. In February, 1888, Striimpell (Deutsch, Archiv f. Nervenheilkunde, 1897) noted a marked glycosuria in one of his cases. In May of the same year the sugar had disappeared. It reappeared in October, then did not return, even after the in- gestion of a large quantity of carbohy- drates. Of the 176 cases of acromegalj^ re- ported so far, 35.5 per cent, included glj'cosuria as a symptom. Experi- ments were made, injecting hypo- physeal extract obtained from men and horses into dogs and rabbits. In the rabbits a glycosuria varying from a slight trace to 4.2 per cent, always occurred. Borchardt (Zeit. f. klin. Med., Bd. Ixvi, S. 332, 1908). In a case reported by the writer the glycosuria was not due to a secretion but to nerve irritation of the floor of the third ventricle by an enlarged sella. Lereboullet (Progrcs Med., Mar. 6, 1920). In 215 reported cases studied by the writer, 91 had thyroid lesions and glycosuria was present in 35 per cent. The pituitary disturbance seemed to precede that of the thy- roid. J. M. Anders (Trans. Med. Soc. State of N. Y.; Jour. Amer. Med. Assoc, June 4, 1921). Dallemagne, Pineles, and von Hansc- mann have found lesions of the pan- creas at the autopsy. The first of these observers, in addition, noted the pres- ence of small gliomatous fonnations in the region of the fourth ventricle. ACROMEGALY (LAUXOIS AND CESBRON). 281 According to Lorand the glycosuria Sajous, relative to nervous irritation, results from disturbance in the internal however, the presence of an interme- secretion of the hypophysis, and is a diary is further required for the produc- component of one of the polyglandular tion of glycosuria. According to some, syndromes, to learn the precise nature this intermediary factor is the pancreas ; of which investigations are now being in the opinion of Gilbert and his follow- conducted. ers, it is the liver which, under these Loeb believes it due to pressure ex- conditions, becomes functionally over- erted on the structures at the base of the active; according to Sajous, it is the brain, and, since, of all cerebral tumors, adrenals, to which he traced nerves those developing from, or in the neigh- from the pituitary, the adrenal secre- borhood of, the hypophysis are the most tion augmenting through increased oxi- likely to cause glycosuria, he is of the dation the production of amylopsin, opinion that a center regulating the which, in turn, increases abnormally metabolism of sugar exists in this re- the conversion of the hepatic glycogen gion. The center discovered by Claude into sugar. Bernard in the floor of the fourth ven- Rath, Oppenheim, Konigshoflfer, and tricle would thus not be the only one of ^\'eil have reported polydipsia together this kind; Schiff, indeed, appears to "^vith polyuria in the entire absence of have found other such centers in the glycosuria. Bouchard has noted pep- optic thalami, crura cerebri, and pons, tonuria and Duchesneau phosphaturia. Eckhardt produced glycosuria in rab- Among the other disturbances of se- bits by injuring the vermis of the cere- cretion, frequent and copious szveating helium, and, returning to clinical and should also be mentioned, pathological records, we may recall that The anatomical and functional Lepine observed diabetes in a case of changes taking place in the reproductive softening of the central gray nuclei, and organs in acromegalic cases were early Loeb and Naunyn in cases of cerebral recognized. The penis, which, as Erb hemorrhage. correctly remarks, is also an ''axpov," According to the views of Sajous sometimes, though not regularly, attains ("The Internal Secretions and the Prin- a greater size than normal. In the fe- ciples of Medicine," vol. i, 1903; vol. ii, male, the clitoris may undergo corre- 1907; Gazette des Hopitaux, Mar. 10, sponding hypertrophy, and the folds of No. 29, 1907), who holds that a nervous skin forming its prepuce may become center exists in the hypophysis, and that thickened. the several ductless glands are con- This enlargement of the genital or- nected by a nervous pathway, a ready gans should by no means be taken to explanation is afforded. Diabetes of imply increased functional activity. In- hypophyseal origin is the result of an deed, male patients usually experience irritation, a disturbance produced in the a diminution of desire and potency, nervous center which the gland con- which may progress to complete loss of tains, in the same way that the nerve- the function. In the female, the most path, in its bulbar course, is influenced important result is suppression of the by puncture of the fourth ventricle. menses, which occurs so early in the dis- Whether we adopt the view of Loeb, ease that in many cases it may be con- involving pressure changes, or that of - sidered the initial event. 282 ACROMEGALY (LAUNOIS AND CESBRON). The primary increase in size in the genital organs soon gives way to a true atrophy. In certain cases of hypophys- eal tumor which had not been accom- panied by acromegaly, the penis was ob- served to have dwindled to the size of the little finger, the testicles to have become small and soft, and the pubic hair diminished in amount. Pechkranz and Babinski were the first to report these changes. Roubinowitch published the interesting history of a patient, previously studied by Pierre Marie, who developed acromegaly after childbirth, and showed progressive atro- phy of the organs of generation. On the basis of published facts we may at present conclude that sexual atrophy can form part of the hypophys- eal syndrome, but that it is not inva- riably a consequence of tumors of the hypophysis. Coming on in youth, these tumors may cause arrest of development of the genital organs; appearing later, they may cause retrogressive changes in them. The problem has not yet been solved, since it will be necessary to de- termine more precisely in what measure the hypophysis is capable of producing genital atrophy. The experiments of Vassale, of Caselli, and of Sacchi seem to have demonstrated that removal of the gland in young animals is without eflfect on their sexual development, but these animals have never survived any length of time. Moreover, a certain number of cases have been known, in- cluding those of Schmidt-Rimplex, of Gotzl and Erdheim, of Babinski (Revue Neurologique, vol. viii, p. 531, 1900), of Pechkranz, and of Bartels, in which the tumor causing genital atrophy did not involve the hypophysis. In our description of the acromegalic dystrophy we stated that the hypertro- phic changes witnessed were due to an abnormal development in the various connective tissues. This overgrowth may, however, be limited to certain parts of these tissues, and in particular to the panniculus adiposus. In 1901, Frohlich (Wiener klin. Rundschau, 1901) drew attention to a special va- riety of adipose overgrowth occurring in cases of tumor of the hypophysis, and attaining considerable proportions. Erd- heim (Ziegler's Beitrage, Bd. 33, 1903) confirmed the association of these two conditions, and a number of cases have recently been reported. The acctimula- tion of fat under these circumstances is steady and more or less rapid. It may reach an enormous extent. With the adipose accumulations are often associated signs of increased in- tracranial tension, and at times, as we have remarked, mental disturbances. We are not as yet in a position to ex- plain the special involvement of the re- serve tissues in this affection, but will have to limit ourselves to recalling the following interesting observation re- ported by Madelung (Langenbeck's Ar- chiv, Ixxiii, p. 1066) : A girl 6 years of age, having been shot in the head, began to put on fat six months later. Her weight doubled in the space of three years and reached 42 kg. (92 pounds). Examination with the X-rays revealed the bullet in the region of the infun- dibulum. Myxedema may form part of the hy- pophyseal syndrome. From the early observation of Norman Dalton (Lan- cet, No. 6, 1897) to that of Sainton and Rathery (Bull, de la Soc. INIed. des Hop., May 8, 1908), a large number of cases have been reported which support the view that this combination may occur. The simultaneous presence of simple goiter and of Basedozi/s disease aas Lipomatous Type of Frohlich's Syndrome. (P. E. Laimois.) ACROMEGALY (LAUNOIS AND CESBRON). 283 likewise been reported. Although the association of these disorders is a point in favor of the existence of a poly- glandular syndrome, it would be rash at this time to attempt to define the latter precisely. The polyglandular syndrome was clearly marked in a case observed by the writer. The right lobe of the th}'- roid showed a distinct enlargement of the colloid type; Addison's was shown by a brownish discoloration of the face and arms and asthenia. Bendell (Albany Med. Annals, Sept., 1915). The writer observed a case of typical acromegalia in which an ex- treme degree of exophthalmos ex- isted along with the von Graefe, Dal- rymple, Stellwag and Gififord's signs of Graves's disease. Weidler (Bos- ton Med. and Surg. Jour., Apr. 6, 1916). Ophthalmic Disorders. — The quasi- positii'c signs of the presence of a tumor of the hypophysis are found in a study of the ocular disorders, which result from the close anatomical relationship of the pituitary gland to the optic path- w^ays. The visual disturbances long ago attracted and retained the attention of investigators. Among the earliest ob- servations should be remembered those of Vieussens (1705), and of RuUier (1823). Ocular disturbances are also mentioned in the papers of Rayer and of Friedreich. Bernhardt has summar- ized them as follows: "Slow, progress- ive amblyopia, terminating in absolute blindness. Since the latter does not re- sult from increased intracranial tension, but is generally due to pressure on the optic tracts, chiasm, and optic nerves, papillary edema is not generally present, primary atrophy taking place in most instances." As for the events related more par- ticularly to acromegaly, Pierre Alarie at first recorded merely optic neuritis in mild cases, absolute blindness in ad- vanced cases; Pinel-Maisonneuve in France, Schiiltze (Berl. klin. Wochen- schr.. No. 38, 1889) in Germany, and, later, Boltz (Deutsche med. Wochen- schr., page 685, 1892), and Packard (Amer. Jour, of the Med. Sciences, p. 660, 1892), sought to emphasize the diagnostic value of bitemporal hemian- opsia, i.e., loss of vision in the lateral Acromegaly with tumor of pituitary and groiter. (P. E. Lannois.) halves of the two visual fields, with preservation of central vision. Since these earlier investigations, numerous observations have been collected; the present tendency, based on these, is even to establish a distinction between tumors arising in the hypophysis itself and those developing simply in the hypo- physeal neighborhood. The former are not, in general, accompanied by pro- nounced disturbances of vision until a rather advanced stage. The morbid change in the optic nerve, however, al- most always progresses, and leads finally 284 ACROMEGALY (LAUNOIS AND CESBRON). to complete amaurosis of one or both of Bassoe (Jour, of Nervous and Men- eyes, tal Diseases, Sept. and Oct., 1903) and The first sign afforded on systematic Yamaguchi. In the case of a young girl examination of the eyes is a diminution who suffered complete loss of vision in of visual acuity. But slightly marked three weeks, Woolcombe (Brit. IMed. at first, this generally undergoes grad- Jour., June, 1896) discovered the pres- ual increase, absolute blindness being ence of an exceedingly vascular psam- reached, in most instances, only after a moma. period of ten or twelve years. Ordi- Of still greater interest and impor- narily,one eye is more seriously affected tance are the alterations in the fields of than its fellow, and shows amaurosis at vision which accompany tumors of the an earlier period. hypophysis, and occur with particularly The condition sometimes runs a rapid remarkable frequency in acromegaly, course; it may disappear for a short From the standpoint of diagnosis they time, then return and become definitely are of primary importance, established. According to Oppenheim In 22 cases with autopsy in which (Berliner klin. Wochenschr., No. 36, changes in the visual fields had been re- 1887, and No. 29, 1888), the histolog- corded, the percentage of each form of ical structure of tumors of the hypophy- hemianopsia was as follows: Bitem- sis, which are frequently very vascular, poral hemianopsia, 23 per cent. ; unilat- bears a casual relation to this "oscillat- eral temporal hemianopsia, 23 per cent. ; ing vision." From the rupture of ves- homonymous hemianopsia, 9 per cent, sels with their walls in an embryonal, Concentric reduction of the visual fields formative state, followed by more or was recorded in 22 i)er cent, of the less extensive hemorrhage, sudden cases; an irregular contraction in 4 per blindness might result. Eisenlohr (Vir- cent.; in 9 per cent., but one quadrant chow's Archiv, Ixviii, p. 461 ) reports the was preserved ; in 13 per cent, there was case of a man who, without having pre- a central scotoma. viously exhibited any pronounced dis- Study of the eye symptoms in dis- turbance, was suddenly seized with lainly appreciated at its posterior wall. Schuller believes that enlargement of the bony cavity is the rule, even where the tumor is of relatively small size, and of slow, regular growth. The bony pa- rietes may, in certain cases, undergo pressure atrophy. In cases of rapidly growing tumor they likewise disappear, being invaded by the neoplastic tissue. Erdheim has established still nicer Diagram of the acromegalic skull, worked out by P. E. Launois and P. Roy, according to the X-ray findings of B<'clere. Shows increased depth of frontal sinuses, irregular thickening of the cranial bones, abnormal projection of postlambdoidal eminence, and enlargement of sella turcica. By combining the above data we were enabled to construct a diagram of the acromegalic skull, as shown in the an- nexed illustration. By taking X-ray pictures from the facial aspect one can likewise learn of the changes occurring in the mandible and the degree of prognathism they may engender. German investigators have sought to attain further precision in their radio- graphic studies. According to von Rut- keroski, each time the hypophysis in- creases in volume the sella turcica very rapidly enlarges in all dimensions ; the distinctions. According to this author, if the tumor remains limited to the sella turcica, the latter enlarges, but its aper- ture above does not widen. If there is a tumor of the infundibulum, the upper aperture may enlarge, but the bony fossa is little altered. Lastly, if the tumor rises above the sella turcica and bulges out over it, the fossa flares out above, presenting a broad superior opening. We may agree with Furnrohr ("Die Rontgenstrahlen im Dienste der Neu- rologic." Berlin, 1906) and Sternberg, that these are altogether too fine dis- tinctions. All those who have had oc- 288 ACROMEGALY (LAUNOIS AND CESBRON). casion to study radiograpliic prints will interior of the cranium, and that the readily understand that it is practically borders of the sella turcica are clearly impossible to appreciate the trifling dif- apparent. Normally a little cup-like ferences of shading upon which such cavity, it becomes so large, when a distinctions must depend. tumor of the hypophysis is present, that Jean-Pierre Mazas, the giant of Montastruc (front and back views). (Brissaud and H. Meige.) It is, nevertheless, a fact that the diagnosis of tumor of the hypophysis cannot today be made without the assistance of the X-rays. If, taking advantage of the improved methods introduced by Beclere, we place in the stereoscopic apparatus a reduced image on glass, we find that the body of the sphenoid is brought out in relief in the the tips of two, three, or even more fingers can be accommodated in it. Relationship Existing Between Ac- romegaly and Gigantism. — The prob- lem concerning the relationship which gigantism bears to acromegaly is one of great interest. Our data are now sufficiently accurate to allow of its solution. ACROMEGALY (LAUNOIS AND CESBRON). 289 In his original description, P'ierre Marie had clearly separated the two dystrophies. Numerous facts, however, were soon garnered which tended to overthrow this dualistic view. The question was in reality brought to a focus by Brissaud and Henri Meige (Jour, de med. et de ^.hir. pratiques, Jan. 25, 1895 ; Nouv. Iconog. de la Sal- petriere, 1897. Meige, Congres de Neu- rol, de Grenoble, 1902, and Archives gen. de Med., Oct., 1902, p. 410. Bris- saud, Bull, de la Soc. Med. des Hop. de Paris, May 15, 1896) when they wrote: "The combination of acromegaly with gigantism is far from being a mere co mcidence, a casual meeting between two distinct pathological states : Gigantism and acromegaly are one and the same disease. \Miat has not been given suffi- cient consideration in their reciprocal relations, however, is the age at which the disease makes its first appearance. If the stage in which the bony over- growth occurs belongs to adolescence and youth, the result is gigantism and not acromegaly. If, later on, after hav- ing belonged to youth, in which the stat- ure is continually increasing, it en- croaches upon the period of completed development, i.e., upon that phase of life in which no further osteogenetic growth takes place, the result is a com- bination or concurrence of acromegaly with gigantism. "Gigantism is the acromegaly of the growing period ; acromegaly is the gi- gantism of the period of completed de- velopment ; acromegalogigantism is the result of a process common to gigantism and to acromegaly, overlapping from the period of adolescence into that of maturity." These constitute three fundamental propositions, which soon received con- firmation from the labors of Woods, Hutchinson and of one of us, published in conjunction with Pierre Roy. As viewed by the adherents of the unicist theory, acromegalic gigantism is that form of gigantism in which the Jean-Pierre Mazas, the giant of Montastruc (profile view). (Brissaud and H. Meige.) characteristic loss of harmony between structure and function finds its expres- sion, to a greater or less extent, in the usual symptoms and deformations of acromegaly, after union of the epiphy- ses to the diaphyses has taken place, whether this union has been prompt or delayed. 1—19 290 ACROMEGALY (LAUXrirs AND CESBRON). Jn the majority of giants almost all the stigmata of acromegaly may be recognized. Sometimes but slightly marked, the significant changes can be detected only upon careful inspection ; presence of acromegaly in the person before him. In the course of our investigations on gigantism we were led to establish a well-defined distinction between two at other times very pronounced, tliey types of giants, viz., the i)ifa)itile giant, attract immediate attention and are in whom the connecting cartilages have Acromegalogrigantism in a Chinaman. (Matignon.) equally as striking as the stature of the individual afflicted with them. The dis- proportionate size of the hands and feet ; the homely, sometimes even repulsive facial aspect ; the evident sagging of the body, which is often marked, make of the subject's gigantic stature a distinc- tion little to be envied, even in the eyes of the layman who cannot recognize the not undergone ossification and are still al)le to proliferate, and the acromegalic giant, in whom these cartilages have be- come ossified and who presents bony thickenings. This distinction, having as its anatomical basis the two separate processes of cartilaginous and perios- teal ossification, though a true one mor- phologically, does not hold good indefi- ACROMEGALY (LAUXOIS AND CESBRON). 291 nitely in time, i.e., the infantile type, having remained pure during a certain number of years, tends to progress toward the acromegalic type, later merging into it completely. We may state, as a general conclusion, that, tumor of the liypophysis can be recog- nized. In 10 cases, taken from among the most recent and the most thoroughly recorded we could find, it was not once lacking. To these direct observations should be added the results obtained Skull of the giant Constantin (profile while all giants are not acromegalics, at least all those who are not such al- ready are apt to become acromegalics. Whatever be the variety of gigantism encountered, a properly conducted clin- ical analysis will disclose the morbid manifestations of the hypophyseal syn- drome. That this is true is due to the fact that /// all giants, whether in life by means of the X-rays, or after death on the autopsy table, the existence of a view). (Dufrane and F. E. Launois.) from studies of the skeletons of giants. Langer reports having found an in- crease in the length, breadth, and depth of the sella turcica in every case, and it is well known that in pathological states, as well as normally, the dimen- sions of this bony fossa in the sphe- noid are those best suited for its con- tents. The general conclusion warranted by all these mutually confirmatory data is 292 ACROMKGALY (LAUXOIS AXD CESBRON). that, whether associated zvith infantilism or acromegaly, yiyantism ahvays occurs in association with a tumor of the hy- pophysis. This assertion cannot, of course, be given as applying to all future observations, but in view of its uniform acromegaly with or without giantism. Tliat the relationship between acro- megaly and giantism is close is shown by the fact that a consider- able percentage of acromegalics are giants and that a still larger percent- age of giants develop acromegaly. Skull of the giant Constantin (anterior view). (Dufrane and P. E. Launois.) confirmation by those of the past it is, at least, very impressive. Hyperactivity of the anterior lobe of the pituitary coming on before the completion of epiphyseal ossification, results in giantism, that is to say, the individual is overgrown but well proportioned. After epiphyseal ossi- fication is complete, however, hyper- activity of the hypophysis results in Symmers (Interstate Med. Jour., Nov., 1917). COURSE AND DURATION.— Established acromegaly is generally observed in adults, male or female. The initial dystrophic phenomena ap- pear at the age of 18 to 25 years, i.e.. at the period in which, under normal conditions, growth is continued and ACROMEGALY (LAUNOIS AND CESBRON). 293 completed. Sometimes it is headache isted, and under these conditions the which leads the std:)ject to consult a question arises in our minds whether physician. Other victims, frightened they could not have created a disturb- at seeing their hands and feet grow ance in the hypophysis, as well as in the larger, come to hnd out the reason other ductless glands. Base of cranium of the griant Constantin. showinsr marked enlargement ot sella tuicica. {Dufrane and F. E Launois.) for these changes. In women the outset of the disease may be traced with some degree of probability to a period at which menstruation became irregular or ceased. We must recognize that such indications are rather vague, as is also the information obtained from the past morbid history. Sometimes in- fectious diseases are found to have ex- The dystrophy seems to occur with greater frequency in women than in men. Taking the combined statistics of Souza-Leite and of Duchesneau,we find 22 men were affected as against 31 women. While the onset of the disease is sometimes delayed (forty-nine years in a case of Schwartz), it can also be pre- 294 ACROMEGALY (LAUNOIS AXD CESBRON). cocious, and the few cases of this kind recorded have made it possible to de- scribe the acromegaly of children or of adolescents. Race is without influence in the etiol- ogy. Acromegaly has been met with in all countries and among all races. Di- Humerus of the giant Constantin Absence of anion of upper epiphysis at the age of 29 years. {Dulrane and P. E. Launois.) rect hereditary transmission has been observed. The dystrophy follows a progressive, but extremely slow course, which can be divided into several stages. The first (stage of onset), in which the deformi- ties begin to develop, is followed by a second (sthenic stage), in which they attain their maximum. In this stage the acromegalic woman ]:)resents a most striking appearance. The increased size of her body, accentuated by hyjx^rtro- phy of the extremities; her peculiar countenance, with the lips, chin, and cheeks frequently covered with long, curly hair, and her low-pitched voice, all combine to impart a masculine ap- pearance, which is sometimes very pro- nounced. In a third stage the hypo- physeal syndrome asserts itself until its manifestations are more or less com- pletely present. The duration of the disease varies within wide limits (twenty to thirty years). In this connection Sternberg recognizes three forms of the affection: an ordinary form, running its course in eight to thirty years, and two rare forms, the one benign, which may last fifty years, the other malignant, des- troying life in three to four years. This last form, seen only 6 times out of 210 cases, is always associated, ac- cording to Gabler, with an epithelial tumor of the hypophysis. PROGNOSIS.— As for the termina- tion, it is fatal. The patient at last in- variably succumbs, either to the effects of a slowly developing cachexia, to in- tercurrent disease, or suddenly succeed- ing an attack of syncope or some cere- bral accident. If acromegaly be associated with in- fantile gigantism, the data at hand are somewhat more precise, and the onset of the disease can readily be referred to the growing period proper. DIAGNOSIS.— The external appear- ances of acromegalics are so character- istic that the diagnosis is at once mani- fest, even from a distance. There are a few disorders, however, wnth which acromegaly might be confounded, and which it is necessary to differentiate. In myxedema, the trunk and extremi- ties show enlargement, which consists, however, merely of an edematous infil- ACROMEGALY (LAUXOIS AND CESBRON). 295 tration of the soft tissues. The thick- ened skin is bound down to the sub- jacent layers and merges into them. The round, pufify face of myxedema dif- fers radically from the ovaloid face of the acromegalic patient, in whom, be- sides, prognathism and kyphosis are characteristic features. In Paget' s disease of the bones (oste- itis deformans) there is increased thick- ness of the cranial bones and more or less marked bowing of the bones of the extremities. The thickened femora and tibia are strongly curved inward and forward, the legs are widely separated, and the trunk and neck are fixed in a position of pronounced flexion. In this affection the bones of the cranium are those involved, whereas in acromegaly the facial bones are rather affected. In the limbs the changes are limited to the diaphyses of the long bones, whereas acromegaly shows a marked predilec- tion for the bones of the extremities and the extremities of these bones. Paget's disease, moreover, seldom ap- pears before the age of 40, and, differ- ently from acromegaly, attacks the va- rious bones v,"ithout order or symmetry. Under the name of leontiasis ossea Virchow described a condition associ- ated with hyperostosis of the facial and cranial bones. The lumpy appearance of the exostoses and the normal propor- tions of the hands and feet are sufficient to preclude all doubt as to the nature of the affection. In erythromelalgia the face remains unchanged. The hypertrophic process involves only the soft tissues of the feet and hands, and is associated with an al- together peculiar cyanotic hue of the integimient. Certain cases presenting a combina- tion~ of the stigmata of rickets and of the lymphatic diathesis might be taken for acromegalics. They exhibit clumsy hands and large feet, the lower lip is thickened and everted, and the face is somewhat puffy. But the extremities show nodal deformities of a special type, wliile prognathism, as well as macroglossia, are completely absent. It is in Iiypertrophic pidmonary osteo- arthropathy, the dystrophic affection seen among inveterate coughers, that confusion with acromegaly most readily arises. Pierre IMarie, Avho was the first to recognize and describe this form of sys- tematized osteopathy, showed clearly, in a striking comparison he made of the two conditions, that the features wherein they differ are more numerous than their points of similarity. In both affections there is symmetrical hyper- trophy of the upper and lower extremi- ties, together with spinal curvature. But in pulmonary osteopathy, the hyper- trophy, which is not uniformly distrib- uted, is associated with distinct deform- ity of the parts affected. The spinal curve is altogether different from that of acromegaly, and prognathism is ab- sent. The changes are strictly confined to the bony tissues. In the hands, the distal phalanges are clubbed, resembling drumsticks ; the nails are lengthened, broadened, curved like a parrot's beak, and show cracks and longitudinal stria- tions. The carpal and metacarpal regions are practically normal. The wrist, how- ever, is thickened and greatly deformed. In the feet, the distal phalanges are clubbed, the tarsus and metatarsus rel- atively normal, and the malleoli hyper- trophied in all dimensions to such an extent that the lower part of the leg is thicker than the middle. In ad- dition, all the long bones of the limbs are thickened, though more markedly 296 ACROMEGALY (LAUNOIS AND CESBRON). in the leg and forearm than in the thigh and arm. The joints are involved in these changes ; their enlargement inter- feres with ease of motion, both active and passive. Furthermore, kyphosis is not constantly present, and when it is present is confined to the lower dorsal or lumbar regions. In the face, the su- perior maxillary bone is alone thick- ened, the mandible remaining normal. In syringomyelia of the pseudoacro- mcgalic type, the hypertrophic process is confmed to the upi:)er limbs and some- times to a single extremity. It does not involve equally all the fingers of a hand. The parts involved arc deformed and exhibit more or less marked trophic changes. The symptoms resulting from the spinal cord lesion are easily recog- nized. As for certain localized liypcrtrophic manifestations (macrodactylia, macro- podia, hypertrophy of a limb, or of one side of the body"), described by Mrchow under the name of partial acromegaly, they are congenital in most instances and bear no relationship to true acro- megaly. PATHOLOGY.— The dystrophic process in acromegaly shows a special predilection for the supporting tissues derived from the mesoderm (connect- ive tissue, cartilage, and bone), to what- ever degree of differentiation they may have attained. The thickening of the integument is due to marked proliferation of its con- nective-tissue elements; the prolifera- tion takes place in each of its various layers. Hyperplasia in the superficial stratum brings about hypertrophy of the papill?e, causing them to appear as pronounced ridges. Similar connective- tissue proliferation takes place in the walls of the sebaceous and sweat glands, in the sheaths of the hair-follicles, in the adventitia of the superficial blood- vessels, and in the nerve-sheaths. These vascular and nervous changes are not without influence on the trophic state and functions of the skin. They like- wise interfere with the nutrition of the cutaneous appendages. The epidermis develops many new layers, especially in the zone of the stratum corneum; the several varieties of hair become thick- ened and kinked, and the nails develop longitudinal striations. Hypertrophy of the teeth has occasionally been noticed. Tlie connective-tissue cells of the sub- cutaneous panniculus adiposus in some cases become overloaded with fatty ma- terial. To this superficial adipose de- posit is added, in the syndrome identi- fied by Frohlicli, a deep-seated adipose accumulation, especially marked in the neighborhood of the peritoneal reflec- tions. Macroglossia is due not only to thick- ening of the mucous covering layer of the tongue, but also to abnormal growth of the interstitial connective tissue. The nasal, pharyngeal, laryngeal, and tra- cheal mucous membranes are likewise the seat of marked proliferation of the connective-tissue elements. The alterations occurring in the fleshy portions of the muscles must also be attributed to clianges of this kind. Thickening of their sheaths and of the septa dividing them into bundles brings about a marked increase in their size. Microscopically, proliferation of the nu- clei and atrophy of the contractile sub- stance are observed. The hypertrophic process extends to the tendons, of which the inserting surfaces become broader, and to the aponeurotic expansions. Among all the changes which the sup- porting tissues undergo, the most char- acteristic, as well as the most marked, are those involving the skeleton ; they ^^^^^^^^^^w^^^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^■H^^K.4 1^^^^ ^^^^^^^^H Molds of the Upper Extremities of a Case of Acromegaly. (P. E. Launois.) ACROMEGALY (LAUNOIS AND CESBRON). 297 are the result of a disturbance in the process of periosteal bone formation. They are met with in the bones hav- ing marrow cavities, and are confined to those of the extremities and those of cancellous structure. They are also found in those membranous bones (cranial bones, inferior maxillary bone) which develop directly from the con- nective tissues, without being preceded by cartilage. Whereas in adult life the periosteum ordinarily ceases to be productive ex- cept under certain experimental or trau- matic conditions, of which a detailed analysis was made by Oilier, in acro- megaly it is seen to proliferate and pro- duce increased thickness of the bones by laying down new osseous layers. Pierre Marie and Marinesco (Archives de Med. Exper. et d'Anat., p. 539, 1891), Renaut and Duchesneau, have made studies of the histological changes occurring in this abnormal type of os- teogenesis. The process is described as "a slow growth of certain bones, taking place at the expense of the periosteal bone, which is reduced to thin layers, while the bony tissue of medullary origin gains in prominence, continues to develop with, so to speak, mathemat- ical regularity, and comes to occupy a predominant position in the structure of the bone. On transverse section the en- tire area is occupied by red bone-mar- row, containing more or less numerous fat-cells. The vessel supplying each medullary space is located exactly in Its center and appears in cross-section. . . . At the periphery of the bone- marrow, in the neighborhood of the open areas corresponding to the giant Haversian spaces of cancellous bone- tissue, the rows of osteoblasts and mul- tinuclear cells which are seen in rachitic bones are here conspicuously absent." Summarizing the above, we may state that, whereas new layers are being added at the periphery of the bone, the central portion is undergoing actual re- sorption by the osteoclasts, the marrow proliferating to take its place. Recently Presbeanu (These de Paris, 1909) had the opportunity, in a case of acromegaly that died as the result of a fall causing multiple fractures, to note the existence of marked demineralization of the bones ; the proportion of ash, which nor- mally ranges between 50 and 80 per cent., had been reduced to 36 per cent. These chemical changes may well ac- count for the weakened condition of the skeleton in this disease. - In infantile giants undergoing transi- tion into acromegaly, the changes in the bones coexist with an altogether abnor- mal persistence of the cartilages uniting the epiphyses of long bones to their di- aphyses. In these cases the bones, while growing in thickness, also increase in length, at least for a certain period. The articulating surfaces of the bones become broader, and the cartilaginous tissues covering them spread out with- out losing in depth. They may undergo some slight alterations in structure, re- calling those seen in the early stages of certain arthropathies. As for the changes occurring in the cardiovascular system, though less plainly evident than those already dis- cussed, they are, nevertheless, well marked. The thickening of the vessel walls and cardiac hypertrophy are due to hyperplasia of the connective-tissue elements they contain. The cardiac muscular fibers may be more or less al- tered. Enlargement of the heart, either simple or associated with a myocar- ditis, is the condition usually found in acromegaly. Sclerosis of the ar- teries and degenerative lesions affect- 298 ACROMEGALY (LAUNOIS AXD CESBRON). ing the walls of the veins, with dila- tation and subsequent obliteration of their lumen, are constantly present. These changes in the heart and ves- sels should be considered as much a part of the clinical picture as the changes in the bones, and they are probably due to the prolonged hyper- tension of the vessels, the result of hypersecretion of the pituitary body. Phillips (Med. Rec, Feb. 20, 1909). The spleen and lymph-nodes some- times appear sclerosed, so greatly has their connective-tissue network become thickened. In a few cases a more or less general- ized condition of splanchnomegaly has been reported, constituting a genuine gigantism of the viscera. The kidneys, si)leen, and pancreas had, in a few of these cases, doubled or even tripled in size. Atrophy of certain viscera, e.g., of the kidney, has been recorded in a few cases ; the appearance of the renal cor- tex recalled that commonly found in in- terstitial nephritis. In the nervous system the connective- tissue proliferation already manifested in the finer peripheral divisions then ex- tends to the deeper branches of the nerves, wdiich present the appearance of thick cords. The sympathetic nerve branches, and more especially the in- ferior cervical ganglion, have been found enlarged and sclerosed. In a case studied by Duchesneau, the peripheral nerves showed changes due to pressure exerted on the spinal roots at the intervertebral foramina. In that of Sainton and State there was bony in- filtration of the dura, with the forma- tion of calcareous deposits on its inner surface, transforming it, in the dorsal and lumbar regions, into a veritable tube of lime. The spinal cord has occasionally been foiuid the seat of connective-tissue pro- liferation and localized or more or less widespread sclerosis. In the brain, the neuroglia, which is also one of the group of supporting tissues, may proliferate more or less actively. The Hypophysis. — Among the changes taking i)lace in the intracranial structures, the most interesting, as well as the most important, are those involv- ing the hypophysis. Connected by a partially hollow stalk with the base of the brain, molded into the sella turcica, which it almost com- pletely fills, held in position by a dia- phragm of dura mater centrally perfo- rated, and weighing on the average 0.5 gram [7^^ grains] in adults, the hy- pophysis has long been considered an ancestral remnant, a rudimentary organ of no importance. According to one of us, the anterior or epithelial lobe of the hypophysis is a gland of branched tubular type. The epithelial tubes or cords of which it is composed undergo anastomosis. In the spaces between them run very broad capillary blood-vessels, with very thin endothelial walls, wdiich must be con- sidered as the excretory ducts. The .glandular cords are made up of epithe- lial cells loaded with granulations. In view of the different staining affinities shown by the latter, the cellular ele- ments containing them may be divided into three classes: 1, acidophile cells, which may be eosinophiles, fuchsino- philes, or aurantiophiles; 2, basophile cells, sometimes called cyanophiles ; 3, chromophobe cells. The protoplasm of these cells is always acidophile. It con- tains, except in the case of the young acidophilic forms and the chromo- phobes, zymogenic granulations, which infiltrate the epithelial elements of the glands. In addition to their acidophilic ACROMEGALY (LAUXOIS AND CESBROX). 299 property, the intracellular granulations possess in common the property known as siderophilia. The primordial cell of the pituitary gland, from the morphological as well as the embryological standpoint, is a small eosinophilic cell with compact nu- cleus and small protoplasmic body, de- void of granulations. This cell develops along two different lines and produces either an acidophilic and siderophilic se- cretion or a basophilic secretion. Two distinct series of cells, therefore, exist in the hypophysis : an eosinophilic se- ries, which becomes siderophilic, and an eosinophilic series, which becomes baso- philic. The products elaborated by them having been eliminated by a semi-, holocrine process, the cells of both series become chromophobic cells, which are capable of undergoing regeneration and of renewing their functional activity. The secretory product of the hypophy- sis is a colloid substance, giving reac- tions sometimes acidophilic, at other X-ray of base of an acromegralic cranium, showing: enlai-gement of sella turcica. {Ch. Infroit.) times basophilic, and which presents analogous features with the material contained in the alveoli of the thyroid gland. We have thought it proper to introduce a summary of this cytologic study, based on our own researches, be- lieving that it may serve as a basis for pathological studies, the results of which thus far have been indefinite and inconstant. Tumor of the pituitary from the giant Santos. (Dana.) On the basis of facts discovered on the autopsy table, which today usually receive confirmation from radiographic studies of the skull during life, we are able to assert,as we have already shown, that hypertrophy of the hypophysis is the rule in acromegaly. We desire to call attention to the fact that in a number of these negative cases the tumor did not originate in the hy- pophysis itself; that this gland was simply compressed or destroyed, and that in a few cases the histological de- scriptions were decidedly lacking in completeness. We must admit, never- theless, that certain of the facts at hand leave room for doubt, which will have to be dispelled by future observations. The gross features of tumors of the hypophysis vary. The size ranges from that of a cherry up to a hen's egg or 300 ACROMEGALY (LAUNOIS AND CESBRON). mandarin. The sella turcica varies sim- ilarly in its dimensions ; its clinoid proc- esses recede from one another, become blunted, and, where an infiltrating neo- plasm is present, sometimes disappear entirely, together with the bony parti- tions they surmount. The tumor not infrequently projects beyond the limits of the bony fossa, not- lial origin, may be variously modified according to the type of neoplasm pres- ent, which may be sarcomatous, angio- matous, etc. The minute structure of tumors of the hypophysis has been variously in- terpreted. The diversity of the descrip- tions given of it results chiefly, if not entirely, from the uncertainty which Tumor of the pituitary body extending into the right lateral ventricle. (P. E. Lauiwis.) withstanding the increased size of the prevailed until within the last few years latter ; it bulges toward and indents the as to the normal structure of the gland, lower surface of the cerebrum, and may It seems to have been shown, how- even infiltrate it to a considerable depth, ever, that, in a number of the cases re- in color the growth is usually gray- ported, the turrior was epithelial in ish, sometimes yellowish ; its external origin. From the 57 cases collected by surface, often granular in appearance, him, Parona has obtained the following may be dotted with small, reddish areas, percentages : — representing dilated vessels or even true Adenosarcoma 45 per cent. hemorrhagic foci. In consistency it is Adenoma 26 " soft and more or less friable. On com- Sarcoma 19.4" plete transverse section more or less ngioma extensive pockets of colloid material These figures, together with similar having a gelatinous appearance may be statistics already published, should be revealed. taken with some reserve, and we must These general features, which belong recognize, with Ilanau, that the condi- more particularly to tumors of epithe- tion of dififuse hypertrophy of the pitui- ACROMEGALY (LAUNOIS AND CESBRON). 301 Cyanophilb Series. wf^ acidosiderophile Series. rrimordial easinophile cell u-ithinU yranula- (iuiis. / SUuhllil tiraaxiliir cyanophile cell. Markedlu granular ciianophilc cell cvn- taininii fat. 1 l>iC7 ! Graviilur eutiinoijhile [■MZ.P' ':''^ cell. V ■ V fi » *ilSirfe^•opfc^7e cell con. ^•. -: / taining fat. 0)ianophile cell con- taining cyanophilic colloid secretion. Siderophile cell containing siderophilic colloid secre- tion. !^ *^^)> Residual chromophobe cell destined to undergo .egen- erution. The two series of secreting cells found in the hypophysis, according to the researches of P. E. Launois. 502 ACROMEGALY (LAUNOIS AND CESBRON). tary bears a marked resemblance to sar- coma. A few of tbe descriptions, however, embody cytological details sufficiently definite to be -of value. Among them may be mentioned the observations of Benda, who found, in three instances, that the hypertrophy was due to pro- liferation of the chromophile cells, i.e., the functionally active elements of the gland. In a fourth case, the neoplasm was undergoing regression. Hyperpla- sia of the same cells has likewise been observed three times by Vassale. Lewis, in an acromegalic case which succumbed to cerebral hemorrhage soon after the onset of the dystrophy, found a pitui- taTy which, while normal in macro- scopic appearance, contained numerous large chromophilic cells. Stud}' of several cases led the author to conclude that pituitary tumors of the adenoma type with cells that do not take the acid stains did not induce a tendency to acromegaly, while the latter was practically always present when the cells were acidophile. Kahlmeter (Hygeia, Ixxviii, No. 10, 1916). Enlargement of the hypophysis may also result from exaggerated growth of its connective-tissue network. Under such conditions the stage of hyperplasia of the organ, associated with expansion of the sella turcica, may be followed by a stage of sclerotic atrophy. The en- larged bony cavity does not resume its former size and appears too capacious for the gland inclosed in it. This condi- tion was found in a case of Huchard, in which the autopsy was performed by one of us. Instead of being generalized through- out the glandular parenchyma, the neo- plastic process may be localized and ap- pear in the form of more or less vohmi- inous masses (partial adenomas, cysts), reaching a variable size [Widal, Roy, and Froin (Revue de Med., Apr. 10, 1906)]. From a general review of the facts yielded by recent investigations, the tend- ency has arisen to accept the conclu- sion that the hyperplastic condition of the hypophysis observed in acromegaly is dependent upon an increase in the number and size and an exaggerated functional activity of the chromophilic cells. This assertion, however, which to us appears premature, cannot, at present, be unreservedly accepted, for a few cases have been seen in which the hypophyseal lesion was not accompa- nied by any dystrophic disturbance. In acromegalic gigantism tumors of the hyj-jophysis are more constantly present than in simple acromegaly. We have already stated, indeed, that in the former condition they have never been found wanting. As for their histolog- ical structure, the same uncertainty pre- vails. To complete this study, we shall men- tion the alterations which the other ductless glands may undergo in acro- megaly : — \\'itli reference to the thyroid, Hins- dale, in a series of 36 cases collected from the literature, found hypertrophy 13 times, atrophy 11 times, while in 12 cases the gland appeared to be normal. Klebs, Massalongo, and Mosse have reported hypertrophy or regeneration of the thymus gland. ^lost observers have failed to inquire into the condition of the adrenals. Their study might prove fruitful, in view of the opinion of Sa- jous that these organs take an active part in the morbid process. PATHOGENESIS.— According to Klebs, who had witnessed persistence of the thymus in a case of acromegaly, the affection is due to an unusual state of de- ACROMEGALY (LAUNOIS AND CESBRON). 303 velopment of the vascular system, and results from an angiomatous condition of the thymus. According to this view, the thymus produces endothelial ele- ments which, swarming through the ves- sels, assume the role of formative cells in the production of fresh vessels. Thus there would result an increase in the number of vascular channels, and, in consequence, hypernutrition and aug- states, at the age when growth ceases, i.e., between the 20th and 25th years. If their functions continue after that age has been passed, acromegaly results. Freund and Verstraeten attribute the dystrophy to a reversal in the normal order of events occurring in sexual de- velopment. "In a certain number of individuals," writes Freund, '"the ordi- nary mode of develooment is disturbed. '■ifK%^j^iJmg^ Cellular characteristics of a tumor of the pituitary. (P. E. Launois, mentation in size of the terminal por- tions of the body, i.e., of those regions of the organism in which the flow of blood slackens its speed. This power to form new vessels, however, which he attributes to the thymus, is as yet lacking in proof. Massalongo has taken up Klebs's the- ory and modified it. He believes acro- megaly to be due to persistence of the functions of the thymus and the hypoph- ysis— organs which play an impor- tant part during fetal life. Normally, these glands undergo retrogression, he Either it lags behind the norm, or else it advances beyond the norm, both in time and in space [i.e., morphologic- ally] ; the malformations which result go hand-in-hand with the disturbance in the development of puberty, and later, too, of the sexual functions." It is certain that the development of the genital apparatus is not without influ- ence on that of the osseous system, and one of us, in a series of communica- tions, has described the alterations pro- duced in the bones by congenital atro- phy of the testicles, of the ovaries, and 304 ACROMEGALY (LAUNOIS AND CESBRON). by castration before puberty. Now, the frequency with which disturbances oi the genital functions are associated with acromegaly has long been noticed. But how is the influence they may exert on the growth of the skeleton to be ex- plained? Perhaps by their suppression, diminution, or modification of a secre- tory product having as its purpose, as suggested by Sajous, to activate the oxidation of phosphorus-containing substances. In short, the development of the geni- tal functions having some influence on that of the skeleton in general, disturb- ances in these functions may be factors in the production of acromegaly, but they do not appear to be sufficient to bring on the dystrophy of themselves. In the opinion of Recklinghausen and Holschewnikow, acromegaly is merely a trophoneurotic afifection, dependent upon changes in the central and pe- ripheral nervous system. Disturbances involving the vasomotor nerves would, according to this view, lead to over- nutrition and hypertrophy of the ex- tremities. There is nothing to indicate, however, that the nervous changes in this dystrophy are primary. The case on which these two observers based their opinion was one of syringomyelia. Pierre Marie looks upon acromegaly as "a kind of systematized dystrophy, occupying in the nosological scale a po- sition about corresponding with that of myxedema, and bearing to an organ of trophic function (the hypophysis) as yet unknown relations similar to those which unite myxedema and cachexia strumipriva to certain lesions and re- moval of the thyroid gland." As this quotation shows, it was the sponsor of acromegaly himself who was the first to suspect the functional role of the hypophysis, "that enigmatic or- gan," as Van Gehuchten termed it not so many years ago. In the preceding pages we have sulifi- ciently dwelt upon the frequency, and even constancy, with which hypertrophy of the hypophysis, especially of epithe- lial origin (adenoma), is present in acromegaly. We pointed out, likewise, a condition which is daily receiving con- firmation from X-ray studies, viz. : that, whatever be the mode of progression of the dystrophy, whether it take expres- sion in its sthenic phase as the pure acromegalic type of Pierre Marie, or the lipomatous type of Frohlich, there is present in most cases enlargement of the sella turcica, which serves to indi- cate hypertrophy of the pituitary body. In view of these facts, while recognizing to their full value the negative cases so far recorded, we are completely in favor of the hypophyseal theory. Having reached this conclusion, we still have to solve two other phases of the problem, viz. : to ascertain the na- ture and mode of action of the disor- ders affecting the function of the hy- pophysis, and to find out whether these disorders are sufficient in themselves, or whether it is not necessary to invoke the synergistic functions of the other ductless glands as participating in the disturbance. The experiments of physiologists, an excellent analysis of which has been given by Paulesco (L'hypophyse du cer- veau, Paris, 1908), have yielded, it must be said, no definite results. Practised upon young or old animals, removal of the hypophysis produced no skeletal dis- orders nor acromegalic manifestations. This dearth of results is not surprising when we consider, on the one hand, the comparatively short period of survival of the experimental animals, and. on the other, the serious traumatism to ACROMEGALY (LAUNOIS AND CESBRON). 305 which they had been subjected in the operations. Of greater weight, as we have already emphasized, are the data afforded by the chnicopathological method. It is on the basis of these data that investigators have sought to ascer- tain the functions of the hypophysis, and, in particular, its trophic role. Some authors, among them Tansk and Vas, and Parhon, consider acro- megaly to be the result of excessive functionation on the part of the pitui- tary— a genuine hypcrhypophysia. Ac- cording to others, the functional role of the gland is to destroy substances toxic to the nervous system. The accumula- tion of these substances, in the presence of functional disturbance of the hy-" pophysis, would produce, because of spe- cial predisposition, a continual state of irritation, resulting in hyperplastic changes in the bony and other support- ing tissues, primarily and chiefly notice- able in the extremities. The acromeg- alic deformities would be an expression of functional insufficiency of the organ, or hypohypophysia. The above hypotheses were those most generally accepted when Hochen- egg published the results of his opera- tions of hypophysectomy. The steady retrogression of the manifestations of acromegaly witnessed after excision of hypophyseal tumors affords an argu- ment of the first importance in favor of the theory of glandular hypersecretion. Future observations will soon bring fur- ther confirmatory evidence. The facts recorded by Hochenegg have also lent considerable support to the doctrine of the synergistic func- tional relationship existing between the ductless glands. In one of his cases, menstruation, which had long since been arrested, returned and was main- tained at regular intervals. In 2 cases removal of the hypophysis was followed by hypertrophy of the thyroid. We have already stated that at the autopsy of acromegalics hyperplasia of one or more ductless glands is frequently found. Furthermore, it is well known that the sexual glands exert a distinct influence on the osteogenetic activities of .the connecting cartilages, and that thy- roid extract is possessed of an analo- gous action. Caselli has expressed his belief in the identity of the functions of the hypophysis and thyroid, basing his opinion on the experimental observation that removal of the hypophysis acts on tetany parathyreopriva in the same manner as does removal of the thyroid. This functional identity, as Souques ("Acromegalie'" in ''Traite de Medecine" of Charcot and Bouchard, 2d ed., vol. x, p. 490) terms it, or, better, this func- tional analogy, would furnish an ex- planation for the power of mutual sub- stitution of function exhibited by these glands under pathological conditions. It was through surgery, practised for curative purposes, that the functions of the thyroid were revealed to us ; it is through surgery that today the role of the hypophysis is being disclosed. It is to surgery, again, that we shall in the future be indebted for the acquisition of positive data which will enable us to solve the absorbing problem concerning the synergistic functional relationship of the ductless glands. TREATMENT.— The treatment of acromegaly necessarily remained, for a long time, purely symptomatic, and was limited to combating the most distress- ing manifestations, such as pain and in- somnia. Agents modifying general nu- trition, such as iodine and arsenic (Campbell), were then brought into use. Iron in large doses and hot baths were said to have given distinct relief I 20 306 ACROMEGALY (LAUNOIS AND CESBRON). in a case under the care of Brissaud. Schwartz claimed to have obtained beneficial effects from the use of ergot. As a corollary to tlie discoveries of Brown-Scquard, opotherapic medica- tion was resorted to. Warda and Pirie tried thyroid treatment without suc- cess, though Lyman Greene claimed, good results with it. Napier admin- istered powdered ovary to an acrome- galic woman wnthout benefit. Kuh, advocates pituitary substance. Tn a case of acromegaly with psy- chic disturbances described by the writer, all the symptoms became con- siderably worse while the patient took pituitary extract, whereas the administration of a thyroid prepara- tion instead coincided witii disappear- ance of the headache, dizziness, and vomiting, and an improvement in the mental state. Renewed pituitary treatment caused all these symptoms to reappear, after which they yielded again to thyroid treatment. Salomon (Presse mcd., Dec. 13, 1913). Favorsky, using Poehl's opohypo- physine, noted distinct improvement in the subjective, and even the objec- tive, symjitoms. The latter observer was able to continue the administra- tion of hypophysine in daily doses of 0.05 to 0.06 (im. (}i to 1 grain) for fifteen months, w'ithout untoward effects. For our part, we have utilized the various animal preparations in a systematic manner and for extended periods, and have been led to the con- clusion that they are entirely in- effective. Beclere, Jaugeas and others have ob- tained amelioration of the pressure symptoms, including ocular phenom- ena by means of X-rays. It has also given good results after operative de- compression. The headache of acromegaly which may become very severe is palliated by the use of antipyrine, acetanilide, or acetylsalicylic acid. Sajous ob- tained contraction of all soft tissues by means of quinine hydrobromide 5 grains (0.3 Gm.) with ergotin 1 grain (0.065 Gm.) t. i. d. and massage of thickened areas. Operative Treatment. — Surgeons eml)oldencd by the increasing safety at- tending their operations, w^ere not afraid to attempt the removal of the hy- pophysis. The anatomical situation of the gland seemed to make the access to it well-nigh impossible. Never- theless, encouraged by the results obtained by physiologists, and hav- ing gained additional information tlu-ough researches on the cadaver, the operators ascertained the avenues of entrance which Avould permit of their reaching the pituitary gland, and on November 16, 1907, Schlosser performed the operation of removing a tumor of the hypophysis from a living person. In theory, the hypophysis may be reached, according to Toupet, either by an intracranial or by an extracranial route. Those who favor the intracranial method advance as their chief argument the less danger of infection to which the patient is subjected, and propose either the frontal route (Krause, Kiliani) or the temporal route, already employed in their experiments by Caselli and Horsley. At the present writing (1918) the chief indication for operation is to re- lieve the pressure of the growth on surrounding important structures. Hence the term "decompression oper- ation" now extensively used. The tumor may be partially removed, or space in neighboring structures of little importance mav be provided to ACROMEGALY (LAUNOIS AND CESBRON). 307 accommodate it if it cannot 1)e re- especially thin in most instances. moved. The tumor may itself alter greatly Special precautions are necessary the shape of the sella and erode its when an operation is to be resorted to. walls sufficiently to penetrate it. A The pituitary, marked with a white cross, can be seen in its dorsal sheath. {U. Proust. ) Both the sphenoidal cells and the radiograph will furnish an outline of sella turcica vary greatly in size, the sella and afford a pretty correct depth, shape and thickness, the pos- estimate of the size and location of terior of the sphenoidal sinus being the growth. 308 ACROMEGALY (LAUNOIS AND CESBRON). A trained brain surgeon should be entrusted with the operation. Some prefer general anesthesia, others local anesthesia, a strong solution of cocain (20 per cent, solution) with adrenalin being used. In the United States two methods have proven fairly satisfactory. The Hirsch-Cushing submucous nasal method and the fronto-orbital method of Frazier. In the Hirsch-Cushing operation intra-tracheal anesthesia is employed. The upper lip is raised and a short incision made down to the anterior nasal spine of the superior maxilla, the soft parts scraped back until the cartilaginous septum is exposed, and the septal membrane then separated on each side as in submucous resec- tion. Upon insertion of a retractor 1.8 cm. in breadth and 6 cm. in length, to separate the freed layers of mucous membrane, most of the vomer, the lower edge of the median plate of the ethmoid, and a small strip of the car- tilage are removed. A series of dilat- ing plugs, up to a diameter of 1.8 cm. are now introduced to flatten the tur- binates slightly, the retractors then withdrawn, and a self-holding, bivalve speculum, with blades about 7 cm. long, inserted. The sphenoidal sinuses having been identified, their anterior and lower walls are chipped away with long-handled nasal rongeurs, the lining mucosa of the sphenoid cells re- moved, and the floor of the pituitary fossa, forming a protrusion into the cells, also chipped away. A\"ith a knife-hook a crossed incision is finally made in the dura covering the pitui- tary^ or growth, and the latter appro- priately dealt with. Termination of the operation consists merely in checking bleeding completely, with- drawing the speculum, and closing the lip incision by means of two or three catgut sutures, without drainage. The 2 layers of septal membrane, as a rule untorn, fall together, and the entire procedure is thus conducted without actually entering the nasal passages. The mode of procedure as regards the exposed pituitary area depends upon the lesion discovered. A mere growth under the sella proper arising perhaps from a pituitary' rest may be removed. If, as is usually the case, the tumor is located higher up and large, even composed of pituitary tis- sue, the sellar decompression des- cribed may suffice to restore vision by relieving the pressure on the optic nerves. A later operation may be- come necessary, particularly if the nature of the growth is in doubt. When a greatly enlarged sella is filled with a large pituitary growth, the por- tion of the latter resting on the sella may be scooped out with but little bleeding. An intrapituitary cyst should be evacuated. Out of 95 operated cases the writer had in Zl subtemporal decompression 2 fatalities, 8 subtemporal explora- tions without mortality, 6 subfrontal explorations with 1 death, 16 tran- sphenoidal decompressions with 3 deaths, and 58 transphenoidal extir- pations, with 4 deaths. The total operative mortality was thus 8 per cent, and the case mortality. 10.5 per cent. In the last ZZ transphenoidal operations there was but 1 death, — a mortality of only 3 per cent. C. Gushing- (Jour. Amer. Med. Assoc, Oct. 31, 1914). In the Hirsch method the middle turbinates are usually removed as a preliminarv^ measure some days be- fore the main operation. At the lat- ter, performed under local anesthesia. ACROMEGALY (LAUNOIS AND CESBRON). 309 the initial incision is made through the mucous membrane over the nasal septum, on one or the other side. Special precautions are taken to in- sure asepsis. The exposure of the pituitary is transphenoidal. as in Cushing-'s procedure. Of 26 cases thus dealt with, 4 succumbed as a re- sult of the operation. The writer employs Hirsch's method with a slight modification; he detaches one of the mucous mem- branes in order to render the spheno- hypophyseal cavity accessible by a nasal fossa. This he deems very im- portant when treating neoplasms originating- from the sella turcica which become extrasellar, and pene- trate into the cerebral cavity and consequently incapable of total extir- pation. The modification is also use- ful where intrasellar growths have a tendency to recur. By insuring easy access to the sphenoidal cavities and keeping in contact with the sella tur- cica, it facilitates the subsequent use of radiotherapy. His 7 cases promptly healed by first Intention. E. V. Segura (Rev. Asoc. med. Argent., xxvii, 984, 1917). Although recognizing the value of Cushing's method and its excellent results, the writer contends that it entails danger of meningitis owing to the fact that the sphenoidal ostia open into the nose. He deems Frazier's fronto-orbital method (see below) more suitable than the sub- mucous procedure in most cases. While Frazier had no mortality in 4 cases, Cushing's series of 16 cases had 1 death. Cope (Lancet, Mar. 18, 1916). In Frazier's operation, or fronto- orbital method, the relation of the frontal sinuses to the supra-orbital margin is first ascertained by transil- lumination. An osteoplastic flap is then formed in the frontal region, the incision starting at the external angu- lar process, coursing through the eye- brow line to the root of the nose, as- cending to within the hair line, turn- ing outward again, and returning to the temporal region on a level with the beginning of the incision. In forming the bone flap the outer por- tion of the supra-orbital ridge is re- moved as a wedge-shaped piece. The periosteum is then freed from the roof of the orbit, the roof removed with rongeurs back to the optic fora- men, and if necessary, a small opening made in the dura to permit cerebro- spinal fluid to escape and thus allow greater displacement of the frontal lobe. The orbital contents are drawn downward and outward, with flat re- tractors, the frontal lobe with its dural covering raised, and the dura then incised horizontally about a centimeter above the base of the skull sufficiently to admit a retractor and expose the contents of the sella. The advantages claimed for the fronto-orbital route are, that it pro- vides an aseptic route, that it allows each step of the operation to be per- formed under direct vision, and that since the primary enlargement of pituitary tumors is towards the brain, the organ is thus an easier object for attack than it is from the infrasellar exposure. For the removal of cysts Kanavel's operation is advantageous. The in- cision is made in the crease of the skin immediately under the nares and alae of the nose. The nasal spine is then cut and the mucous membrane care- fully raised from the floor of the nose and off of the septum, back to the sphenoid bone and off from the front of the latter. The pituitary is then exposed through the sphenoid as in Cushing's operation. In the first of Kanavel's cases the cvst found was no ACROMEGALY (LAUNOIS AND CESBRON). thoroughly curetted, witli the result of bringing the existing typical Froe- lich syndrome to a standstill and re- lieving the marked signs of intra- cranial pressure. Dried pituitary gland was fed for over 3 years. Six ous titles such as epithelial tumors of the infun(lil)uluin, papilloma of the choroid plexus, cystic endothelioma of the pia, adenoma, adenosarcoma, dermoids, etc. The epithelial inclu- sions forming the starting-point of such tumors reach the pituitary from Chiasm Optic nerve. Ojihlhalinie arterij. Pituitary body. OUaetory bulb. Inferior wall of spheiiiiiilal sinus. Relations of pituitary body, as exhibited by removal of llie l)ony floor of anterior cerebral fossa. (Froust ) years after the operation the patient was still living and well. The second case succumbed to meningitis after the oi)eration, while the third was op- erated upon on 3 successive occasions for pressure relief, with ultimate recovery. Three years after opera- tion there had been no recurrence of symptoms. These cysts actually arise through inclusion of buccal epithelium in the hypophyseal region, the remains of Rathke's pouch, e.g., persisting near the infundibulum and later prolifer- ating to form cystic or adamantine tumors, hitherto reported under vari- the craniopharyngeal duct, which in the emhrjo forms a passage from pharynx to brain cavity traversing the sphenoid bone. Kanavel (Surg., Gynec. and Obstet., Jan., 1918). As previously stated, X-ray treat- ment is often resorted to advan- tageously by Gushing after operations, when the growth tends to enlarge rapidly or to recur. The exposures are made throitgh the nares and over the temple on alternate days. Different measures should be adopted under different circumstances: (1) comparatively small tumors in the sella turcica covered with a tent of dura ACTINOMYCOSIS (LAPLACE). 311 mater can be removed completely by the nasal route; (2) growths growing endocranially, but filling the sella tur- cica, can be removed in part to relieve the pressure symptoms, though not the acromegaly; (3) endocranial growths, removal of which can only prove harm- ful. Hochenegg (Deut. Zeit. f. Chir., Bd. c, S. 317, 1909). Confirmation of Paulesco's obser\-a- tion that simple di-'ision of the stalk of the pituitary is as fatal a procedure as removal of the latter organ also, and also of the view that the latter procedure in animals is invariably fol- lowed by death within a few days. This fatal result is evidently due to re- moval of anterior or epithelial lobe, since removal of the posterior or neural lobe is followed by no characteristic svmptom. Cushing and Red ford (Johns Hopkins Hosp. Bull, April, 1909). P. E. Launois AXD M. H. Cesbrox, Paris. ACTINOMYCOSIS.— D E F I NI- TION. — A parasitic, infectious, and inoculable disease due to the develop- ment of the actinomyces, or ray fungus. First described in 1877 in cattle by Bol- linger and in man by James Israel ; it can no longer be considered a rare dis- ease. From its frequent development in the lungs it has often been confused with tuberculosis. SYMPTOMS.— The symptoms vary according to the locality of the disease. The affection is chronic and exception- ally rapid. The granulation tissue is abundant and the mass resembles a tumor. Previous to suppuration it is quite farm, and, if progressing rapidly, is surrounded by diffuse edema. Pain and tenderness hardly ever exist. When suppuration occurs the mass increases rapidly in size. Actinomycosis may develop in almost any part of the body, but Poncet and Berard showed, after an investigation of 500 reported cases, that the sites of predilection were relatively as follows : Head and neck, 55 per cent. ; thorax and lungs, 20 per cent. ; abdomen, 20 per cent. ; other parts, 5 per cent. In France the face and neck were aft'ected in 85 per cent, of the 66 cases reported. Actinomycosis should always be considered in the diagnosis in the case of any newly formed subacute or chronic swelling in the region of the mouth, face, neck, thorax, or right side of the abdomen. Pus from every abscess should be examined as a routine practice. In any subacute or chronic lesion, the discharge needs to be examined repeatedly. Peribuc- cal infections comprise the majority of the cases. Cope (Brit. Jour, of Surg., July, 1915). 1. Cutaneous Surface. — Usually, a lesion of the skin is secondary to the evolution of an underlying actinomy- cotic tumor, which, by its growth, bursts through the skin. A sanguineous or purulent liquid, containing the charac- teristic grains, issues from the ulcera- tions so formed. The grains are small, opaque, yellowish-white, or yellowish masses about as large as a pinhead, which are composed of smaller grains, measuring about %o i^ii^''- These smaller grains are formed by a central mass, of interwoven or straight fibers, whence ex- tend toward the periphery spoke-like prolongations, with club-like termina- tions. Rarely the affection may develop primarily on the fingers, hand, nose, or face. It forms a small, round, ligneous mass, which may soften in a few weeks, burst through the skin, and give a gran- ulous and varied pus, containing actino- mycotic granulations. The border of the granulation is uneven, violet-hued, and undermined. Around the original mass there arise secondary masses ; so that the entire lesion forms a violet-red, in- 312 ACTINOMYCOSIS (LAPLACE). (lurated patch, deeply adherent, and somewhat resembhng scrofuloderma. In cutaneous actinomycosis the lym- phatic ganglia are usually not enlarged. Pain is, in some cases, intense ; in other cases it is awakened only by pressure. The pathognomonic spots, which are more or less deep in color, according as the general color of the lesion is more or less pronounced. If the general color is pale, the spots are bluish red or violet ; if the tint of the mass is deeper, the spots present a blackish or slate color. These s])ots vary in size from that of a pea to tliat of a pin's head. They ap- pear to correspond to the points at wdiich the wall of the abscess is thinnest, and it is here alone that fistulse form. In some instances, as in the case re- ported by Pringle and illustrated in the annexed colored plate, the lesions may assume the appearance of large sarco- matous-looking growths, ulcerating at various points, situated upon hard, brawny, and deeply undermined skin and from the ulcerative points of which pus exudes, mixed with characteristic yellow granules, actinomycosis. 2. Alimentary Canal. — Teeth. — The fungus has been found in carious teeth (Israel), often side by side with lepto- thrix (Senn), or almost pure culture with no manifestation of disease except chronic periodontitis (Partsch). Cari- ous teeth have increasingly been shown to act as etiological factor of the afifection. Tongue and Tonsils. — In man three cases of this afifection have been found on the tongue, one of which was of pri- mary development ; the other two are believed to have found origin in a ca- rious tooth. The tonsils may also be affected and be the seat of white projec- tions resembling masses of moss, which seemed to grow in the crypts. The pharyngeal wall also shows these white masses, as a rule. Lingual actinomycosis in cattle ap- pears as a nodular tumor, with prolon- gations into the parenchyma, of ligneous hardness. Jaws. — The lower jaw is the most frequently affected. At first the disease resembles periosteal sarcoma, until the loose tissues of the neck are reached, when it often rapidly extends downward along the subcutaneous connective tis- sues and intermuscular septa. Accord- ing to Poncet, an early sign of actino- mycosis in this location, in some cases, is a marked difficulty in opening the mouth, long before the presence of the disease can be determined microscopic- ally. , The upper jaw is rarely primarily affected. It then tends to attack rapidly the adjacent parts, and even the base of the skull and brain. A primary actinomycosis infection of all salivary glands can take place. The disease in the early stage has a definite clinical as well as pathologic picture. In a relatively short time the writer observed 9 primary cases. Eight of these were very early cases of primary actinomycosis of the sali- vary glands. Altogether he reports 31 cases, 7 of which originated from the submaxillary gland. The infec- tion entered positively by the duct route in some of the cases and prob- ably in the others also, the patient chewing a stem of grain bearing the actinomycotic organism. Three dif- ferent stages are observed: a diffuse inflammatory process, a localized abscess, and a spreading abscess within the gland, eventually forming new abscesses and finally breaking through with the formation of fis- tulae, either external or internal. G. Soderlund (Nord. med. Ark., xlvi, No. 4. 1914). 3. Intestinal Canal. — The disease be- gins with a sharp, lancinating pain in n p o 5 S < o oq a 3 s ACTINOMYCOSIS (LAPLACE). 313 the abdomen and follows the course of chronic peritonitis. Swellings form- ine abscesses are found on the anterior abdominal wall, which sometimes communicate with the intestine. It may also start from the vermiform appendix. There have also been cases of primary actinomycosis of the colon with metastatic deposits in the liver. Actinomycosis of the intestines is characterized by extensive induration due to a marked development of peri- toneal adhesions and to the exten- sion of the process to the abdominal wall and neighboring organs. As be- fore mentioned, the tendency to the formation of the fistulse is marked. Metastatic involvement of the liver is not unusual. G. S. Towne (Albany- Med. Annals, June, 1917). An acute or chronic inflammation of the appendix may open the door for the entrance of the actinomycotic organism. In general, actinomycosis is practically never carried by the lymphatics and but rarely by the blood stream. The method of exten- sion is by continuity of tissue. Thus it is that general actinomycosis, un- like tuberculosis and blastomycosis, is extremely rare. Many of the ab- dominal organs may become in- volved, as extension of the process usually takes place through retro- peritoneal tissues, sometimes de- stroying muscles and even bones. The early diagnosis of actinomy- cosis is generally overlooked. A firm swelling, painless on pressure, oc- cupying either the right or left in- guinal regions, usually the right, is the sign most frequently found in intestinal actinomycosis. J. W. Keefe (N. Y. Med. Jour., Nov. 30, 1918). There are 3 types of actinomycotic infection of the appendicocecal re- gion, the first with a painless tumor in the right iliac fossa with ultimate formation of abscesses and fistula; the second simulating acute appendi- citis, with the appendix usually found gangrenous at its base; and the third with an infected patch in the cecum, which perforates, giving rise to secondary generalized periton- itis. The writer's case was of the third type, in a woman, Z2 years of age, with recurrent pain in the right iliac fossa for 2 years. Much pus was found in the pelvis and the cecum showed a thickened patch with cen- tral perforation. The normal appen- dix was removed, the cecal patch with its subsequent invagination was scraped, and the peritoneal cavity ir- rigated with saline solution by means of Carrel tubes, removed on the third day. Under potassium iodide, 50 grains {2).Z Gm.), 3 times a day, the wound healed, and the patient recov- ered. E. G. Slesinger (Lancet, June 5, 1920). 4. Genitourinary Tract. — The uterus may also become invaded by the disease, the first manifestation being the dis- charge of a turbid, fetid fluid contain- ing the characteristic shreds and masses. The gross macroscopic and micro- scopic picture resembles that of tu- berculosis in many cases. Bollinger's desideratum for the diagnosis of actinomycosis, namely, that corpora flava must be present, is untenable at the present time. Repeated bac- teriological examinations, and some- times long and tedious ones, of the same specimens must be made to insure a correct interpretation of sus- picious pathological material. Inocu- lation with pure cultures into the ani- mal is not attended with success. Only the injection of pus with actino- mycosis, or the ingestion of material upon which actinomjxosis is grown, will prove successful in the produc- tion of actinomycosis in the animal. Actinomycosis does not travel bj^ the lymphatics, and probably not by the blood route. The prognosis is favor- able in circumscribed cases, which is most likely the condition in which we find the uterine appendages. The treatment consists in radical extirpation and free drainage, the application of tribromphenolbismuth, or irrigation of the fistula with cop- per sulphate. The internal adminis- 314 ACTINOMYCOSIS (LAPLACE). tratioii of larj^c doses of potassium iodide up to 75 grains a day, whicli exerts a positive healing efifect. Carl Wagner (Surg., Gynec. and Obstet., Feb., 1910). 5. Respiratory Tract. — In bronchitic actinomycosis the affection is less severe in winter than in summer, which is the contrary of what is observed in ordi- nary bronchitis. It can be classified in three groups: (1) lesions of chronic bronchitis; (2) miliary actinomycosis, and (3) cases with bronchopneumonia and abscesses. The lower lobe is at- tacked more frequently than the upper ; the opposite is the case in tuberculosis. Actinomycosis of the lungs is found in 20 to 30 per cent, of all cases of actino- mycosis. It probably originates in the mouth, and usually takes the form of bronchitis or bronchopneumonia. In a personal case of actinomycosis the patient seemed to have merely pneumonia except fo- a tender point on one rib and this swelled a little. The surgeon was rather skeptical when called on to open this small tumor, but this revealed typical actinomycosis. Hamburger (Uges- krift f. Laeger, Apr. 25, 1918). 6. Brain. — Here, tumor-like symp- toms exist during life, with headache, paralysis of the abducens, congestion of the optic pa])illa, and attacks of tmcon- sciousncss. In a case reported by Ran- son the autopsy indicated the probable mode of infection of the orbit and brain. A sinus was found leading from the orbit to the gum of the upper jaw ; the ray fungus had probably lodged in or near a tooth, as it has so often been found to do. The fungus was probably carried into the system on an ear of corn chewed at harvesttiine. Having reached the orbit, it crept along its outer wall and in the w^all of the right cavern ous sinus to the base of the brain, ulti mately setting up meningitis and small abscesses, and burrowing through the pituitary body and sella turcica to the cavernous sinus of the left side. The orbit is very seldom the scat of actinomycosis. A case is reported from von Brun's clinic, and 9 cases are cited in detail from the literature. The author's case was the first to be operated upon by temporary resec- tion of the upper part of the cheek- bone, a procedure which is consid- ered superior to Kronlein's resection of the lateral portion of the orbit. The chief symptoms were exophthal- mos and failure of vision in the af- fected eye. There was also lack of mobility of the eyeball. These symp- toms are, however, not pathognomo- nic of actinomycosis, it being essential to an exact diagnosis that the ray fungus be found in the pus. As soon as a diiignosis is made, or there is a well-grounded suspicion of this dis- ease, steps should be taken to radi- cal!}' remove the focus of infection. Miiller (Beitrage z. klin. Chir., Bd. 68, II. 1, 1910). DIAGNOSIS.— When the process is very rapid, actinomycosis may stimulate acute phlegmonous inllammation and os- teomyelitis, or, when widespread, sy[)h- ilis. Sarcoma. — This form of neoplasm does not suppurate or break down so early. In the jaws it is to be dift'erentiated from dental aff'ections : epulis. Tuberculosis. — In this disease the lymphatic glands are infected, and the apices are usually the first involved. In actinomycosis of the lungs the causative organism may be found in the sputum and in the discharges from fistuhe in the chest wall. In sputum the parasite is distinguished from the common leptothrix of the mouth by the fact that the filaments of the latter are larger, straighter, and thicker, do not branch, and are fre- quently adherent to epithelial cells. ACTINOMYCOSIS (LAPLACE). 31 010 Carcinoma. — The skin or mucous membrane involved is in close connec- tion with the tumor; in actinomycosis the skin will be found broken on micro- scopical examination. Syphilis. — A gumma will, in two or three weeks, be sensibly affected by large doses of potassium iodide, which does not act so rapidly in actinomycosis. Lupus. — The diagnosis depends, in this condition, upon microscopical ex- amination. The writer was able to differen- tiate actinomj'cosis by the seroreac- tion in 8 cases, the only negative reaction being in a case in which the cure had been complete for over four 3'ears. The specific reaction is both_ by agglutination and by fixation of complement by. means of the spores of the sporotrichum. Actinomyces cultures cannot be used for the tests, but the generic reaction with sporo- thrix spores is constant and lively. It is specific for actinomycosis, sporo- trichosis, and thrush, but these can be readily distinguished. Widal (Bull, de I'Acad. de Med., May 10, 1910). ETIOLOGY.— Both men and ani- mals are probably infected from vege- tables or water (Israel), from eating ears of barley, or rye, when the fungus penetrates through the wound or abra- sion thus provoked, or in many cases through carious teeth. Intestinal acti- nomycosis is due to taking contaminated food or water, when the fungus be- comes implanted upon an already dis- eased tissue, multiplies, and causes ac- tive proliferation of the submucous tis- sue. It may be transmitted by kissing, as in a case reported by Baracz. Farm- ers should be warned against the habit, so common among them, in chewing bits of straw, wheat, oat-chass, etc., the most prolific cause of the disease. Ac- tinomycosis is frequently met with in shoemakers. This is due to their habit of placing their needles in their mouths (Ullmann ). The disease occurs not only in cattle, among- which it gives rise to the condition known as "big jaw" or "lumpy jaw," but is met w-ith also in hogs. In a case reported by Guinard actinomycosis of the lower jaw was acquired by a toothbrush-maker from holding washed hogs' bristles in the O ■CD mouth before inserting them into the holes in the toothbrush handles. No one has satisfactorily demon- strated the parasite out of the lesions, and nothins: definite is known con- cerning its habitat in the outer world (Towne). The disease occurs nearly three times as often in the male as in the female sex. In a study of a large series of cases, Erving found the youngest case re- ported to have been a child 6 years old ; the oldest was a man of 70. ]\Iost cases were in middle life. Thirty six per cent, of the patients had much to do with live stock or grain. In 62 per cent, of the cases the disease lasted over six months. The disease is a combination of ab- scess formation and new growth of connective tissue. In most cases the disease has the character of a sub- acute or chronic suppurative process, but in some cases the new growth of connective tissue may be so marked a feature of the process that it may present the character of a tumor or neoplasm. G. S. Towne (Albany Med. Annals, June, 1917). Direct infection from the flesh or milk of affected animals, i.e., from tis- sues or products other than the part actuallv diseased, does not occur, ac- cording to evidence so far obtained. Only 6 cases of actinomycosis of the ovary are on record, and none of these are primary. Case of the 316 ACTINOMYCOSIS (LAPLACE). latter kind in a patient who had Hved in London for 16 years, but in 1903 and 1904 was brought into contact with hay, straw, and corn, the usual sources of actinomycosis, and it is noteworthy that the symptoms date from 1904. The streptothrix must have reached the ovary by way of the blood-stream. Taylor and Fisher (Lancet, Mar. 13, 1909). The writer has observed a number of cases in which latent actinomy- cosis was roused to active prolifera- tion by some intercurrent trauma. He has also found similar instances in the literature. There may be an interval of years between the trauma and the manifest actinomycotic proc- ess; in one case seventeen and in another ten years had elapsed, and intervals of five and ten years are by no means uncommon. Noesske (Med. Klinik, Mar. 27, 1910). PATHOLOGY.— The actinomyco- ses were formerly thought to be mold fungi (hyphomycetes), but Bostroem, in 1885, proved by cultivating- them that they were a variety of cladothrix, belonging to the schizomycetes. At present the parasite is considered to belong to the streptothrix group, and the name Streptothrix actinomy- ces has been applied to it. The actinomyces fungus can be cultivated in ordinary nutrient broth to which a few drops of fresh human blood have been added. It is advis- able to sow the material in two broths, one of which is covered by a layer of oil 1 cm. deep. After in- cubation for a few days, the fungus appears at the foot of the tube in small white pufTballs. From such a growth a vaccine can be prepared. In 2 cases in v/hich a vaccine of the homologous organism was employed improvement resulted. Gordon (Brit. Med. Jour., Mar. 27, 1920). The mass is made up of granulation tissue, which, except for the presence of the ray fungus, would be mistaken for a round-celled sarcoma. Epithe- lioid elements and giant cells are also seen. In the granular mass, or in the pus coming from a case of actinomy- cosis, the fungus itself appears under the form of small, yellow, brown, or even green masses, about a pinhead in size, which, on microscopical examina- tion, are found to be composed of a central interwoven mass of threads, from which radiate club-shape-ended rays ; in some specimens certain rays project far beyond the others. In man the clubbed bodies are frequently ab- sent (Senn). The histological lesions are alike in the actinomycotic nodule and in the tuberculous follicle ; only the foreign body diflfers. Water or a weak solution of sodium chloride causes the rays to swell enormously and lose their shape ; ether and chloro- form seem to have no action. At a certain stage there are in every colony three elements, viz. : — 1. Club-shaped formations. 2. A centrally placed network of fungus filaments of varying shape and size. 3. Fine coccus-like bodies (spores), which originate from the fungus fila- ments, and grow into long rods and branching twigs. Two types, the typical and atypical, should be recognized, according to BerestnefT. Typical actinomycosis is the disease in which occur the charac- teristic mycelial masses, having club- shaped radiations. Atypical actino- mycosis includes such diseases as Xoc- ard's farcin dc bariif, and infections which clinically and anatomically re- semble actinomycosis, and are caused by mycelial organisms w^hich corres- pond quite closely to the cultural peculiarities of the streptothrix ac- tinomyces, but fail to form the char- acteristic grains in the tissues and pus. ACTINOMYCOSIS (LAPLACE). 317 Case of streptothricosis, a disease of man or animal due to one of the various forms of streptothrix. The manifestations of the disease probably differ in accordance with the forms of causative organism. If organisms of thread form are present the surgeon can be reasonably sure of the diagnosis. If the threads are branched he can be certain of it. The ray fungus is sel- dom found in humans, and is not in- variably found in bovine streptothricosis. The appearance of the disease varies with the stage in which it is seen. A description of the surface appearance of an early stage would by no means fit a well-developed or an advanced case. The appearance is greatly changed by mixed infection with pyogenic bac- teria. A severe secondary pyogenic infection may obliterate all appearances suggestive of streptothricosis, and in " such a case it may be impossible to demonstrate the streptothrix. Certain persistent abscesses, particularly ab- scesses connected with the alimentary tract, are due to streptothrix infection and secondary infection with pyogenic bacteria. J. Chalmers Da Costa (An- nals of Surg., July, 1911). Staining. — The following stains have been used : — Wedl's orseille (Weigert). Eosin (Marchand). Cochineal — red (Danker and Mag- nussen). Hematoxylin alum (Moosbrugger). Gram's method — section staining (Partsch). Safranin in aniline oil, followed by K. I. (Babes). Solution of orcein in acetic acid (Is- rael). Picrocarmin — fungus, yellow; other parts, red (Baranski). The actinomyces in a section are best shown by Gram's method, first with methyl violet, then with Bismarck brown (Tillmann). Cultivation. — It is quite difificult to cultivate in coagulated blood-serum (O. Israel), coagulated blood-serum and agar-agar (Bostrom), and coagulated egg-albumin and agar-agar (Wolff and J. Israel). INOCULATION.— It has been suc- cessfully carried out by James Israel and Ponfick, from tissue and from pure cul- tures. Opinions differ as to its power of producing pus, a secondary infection by the pus-germs being thought the true cause of the pus sometimes found with , . 1 . • , ' a 0, Ray-funeus or masses, showing central myce- lium of actinomycosis, b, White blood-corpuscles, showing their relative size. (Poncet and B<'rard.) actinomycosis. Dissemination by the lymphatic system never occurs. Glan- dular enlargement indicates secondary infection. 1. Cutaneous Surface. — Around the primary lesion are small secondary le- sions. Two forms are described: (a) The anthracoid, which pursues a rapid course, with fever, and sometimes sep- ticemic in character. It is characterized by flat tumefaction, with multitudes of small openings with yellow granula- tions, from which thick pus exudes. (b) The ulcerofungous, which pursues a subacute course, with tendency to chronicity. In the face it tends to form 318 ACTLKOMYCOSIS (LAPLACE). burrowing abscesses instead of recog- nizable tumors. 2, Bronchial Tubes and Lungs. — Some observers believe that the peri- bronchial lymphatic vessels and glands disseminate the fungus or its spores in the lungs ; when the fungus reaches the lung-tissue proper, granulation tissue is formed, which, through secondary in- fection, suppurates. Amyloid degenera- tion of other organs may occur, or There is widespread induration due to peritoneal adhesions, with exten- sion of the disease to the abdominal and nearby organs, including not in- frequently the liver. Actinomycotic growths in the liver in man, according to Crookshank, have a characteristic naked-eye appearance, from their peculiar honeycombed struc- ture. The cases between the fibrous tra- beculae are full of caseous matter, in. • , 9 0 a O CL 2^0 >«« --is>' ..■--..•.■;:.••;•• <**-p .'■'■'■ ■ ■•'■••' •'•■•Mr- ^"^^^--f- ^1' Kayfungrus {c.c.c), club-shaped bodies (d.d.d). and spores (.a, a, a) found in the pus of actinomycosis. (Poiuxt arid Jii'rard. ) metastasis of the disease, in case a pul- monary vein has been pierced. At times the pericardium or peritoneum becomes affected ( Striimpell ) . 3. Alimentary Canal. — In the jaws the mass usually resembles a sarcoma, but, if incised before secondary infec- tion and suppuration has occurred, the reddish surface wall be seen to be inter- mingled with yellowish spots, which are collections of actinomyces. In the intestines the fungus causes proliferation of the submucous tissue, and whitish patches. External fistulae are commonly found. which the more or less spheroidal masses of the fungus are imbedded. In museum specimens, which have been for some time preserved in spirit, the con- tents of the loculi may have fallen out, and the honeycombed appearance is then much more marked than in recent speci- mens. PROGNOSIS.— The prognosis is se- rious in proportion to the rapidity with which suppuration occurs. Actinomy- cosis of the upper jaw is more serious than actinomycosis of the lower jaw, as it has a greater tendency to invade the deep structures. Internal actinomycosis ACTINOMYCOSIS fl.APLACE). ' 319 is almost always fatal, owing to its in- surgical intervention is resorted to, es- accessibility. External actinomycosis ]Kcially when the disease is so extensive may cause death from pyemia, septice- as to prevent complete removal by surg- mia, and exhaustion. When so placed ery. The results obtained from iodide as to be easily removed and treated of potassium have been remarkable in early the prognosis is favorable. A per- some cases and negative in others. This manent recovery usually follows a com- divergence of views, according to Per- plete removal of the primary focus, as net, depends on the variation in the vir- metastasis is rare (Senn). ulence of the disease, in its evolution in Actinomycosis has a pronounced tend- different individuals, in the difference ency to spontaneous recovery except in existing in the receptivity of the tissues, internal organs (Schlange). and on the influence of secondary in- From an analysis of 60 cases the fol- fective processes. In recent and purely lowing conclusions are reached : When actinomycotic lesions the results may be the disease involves the head and neck, excellent; in old-standing cases, and except in a few cases when the base of where the ray fungus is associated with the skull is invaded, the course is favor- streptococci, staphylococci, and the bac- able, recovery taking place in from three _ terium coli commvme, the drug treat- to nine months. It is exceptional for ment is less successful, the fistula to persist or to form anew According to Berard, in two-thirds after the lapse of a year. Pulmonary of the cases of chronic actinomycosis of actinomycosis may terminate in recov- the face and neck the results of iodide ery. The prognosis of actinomycosis is treatment are ////. In three-fourths of the more favorable, as the anterior ab- the recent cases recovery has been ob- dominal walls are involved and the tained by it, combined with surgical posterior escape. Death usually results treatment, and in one-fourth by iodide from amyloid degeneration and wasting, treatment alone. Potassium iodide can- If actinomycosis presents pyemic mani- not be regarded as specific in actinomy- festations, a fatal termination is to be cosis in man. If, at the end of some expected, as a number of vital organs weeks, improvement is slight only, oper- are likely to be involved. Actinomy- ative interference should be carried out cosis may pursue a chronic course, at once. continuing thirteen years or longer, if The drugs which are the most sue- functionally important organs be not cessful in pulmonary actinomycosis, in involved, as when the process confines the opinion of Sabrazes and Cabannes, itself to the connective tissue about the are potassium iodide and eucalyptus, spinal column. According to Bevan if there is any involvement of chest the prognosis is now much better than ^vall, surgical treatment should be formerly, some cases recovering spon- undertaken. taneously. If surgical treatment is Incision alone will not cure the not possible the prognosis is grave, but condition; there should also be given not alwavs hopeless. large doses of potassium iodide and TREATMENT.-l. General.-Po- f ^^. P^'" 7^!" ^°^"!.'°^ of iodin may be injected into the region ot the tassium iodide was found useful in j^^j^^ irrigation of the incisions animals by Thomassen and Nocard. In ^nd sinuses with diluted tincture of man it should be thoroughly tried before iodine is also of value. Both cases 320 ACTINOMYCOSIS (LAPLACE). were treated in this mannLT aiid re- covery was fairly prompt with little scarring. E. D. Telford (Brit. Med. Jour., Oct. 9, 1915). The injection of a 5 per cent, solu- tion of permanganate of potassium into the cysts has been of advantage. Six cases of actinomycosis appar- ently cured by injections of sodium cacodylate. On the first day a 10 per cent, watery solution (V4 of a Pravaz syringeful) was injected intramus- cularly in the nates, increasing each day Vi syringeful until a full syringe- ful is given during one week, and then decreasing the quantity to the 1/4 syringeful, and then commencing over. The local measures are con- fined to puncture or little incisions for abscesses. More extensive opera- tions are avoided. Foedcrl (Zcn- tralbl. f. Chir., Bd. xxxv, p. 45, 1908). Many cases remain uncurcd no matter what is done. Such a severe case was treated by the writers with daily subcutaneous injections of sodium cacodylate, beginning with IV^ grains (0.1 Gm.), increasing to 15 grains (1 Gm.) and then again de- creasing. The infiltrated mass was incised and into the surrounding 25 per cent, iodipin was injected twice, the second injection being given 2 weeks after the first. In a few months the wound was completely healed with hardly a scar. Bittner and Toman (Prag. med. Woch., Nu. 27, 1913). Case of facial actinomycosis which was cured by the administration, at weekly intervals, of 4 doses of vac- cine, each containing 25 million frag- ments. Combined with this was the opening of the abscess and its curet- tage with dry gauze. C. W. Dean (Brit. Aled. Jour., Jan. 20, 1917). The writers found methylene blue a specific for Actinomyces in the test tube, and used it in a clinical case, which cleared up under the treatment. Either Roentgen ray or radium is probably sufificient as a curative agent. Jensen and Schery (Jour. Amer. Med. Assoc, Nov. 27, 1920).- 2. Surgical. — Local measures which do not completely remove the infected tissues do harm, as they frequently give rise to secondary infection, rapid extension, and death. The best treatment of actinomy- cosis in the writer's hands has con- sisted in the removal of the primary focus, and as much of the infected tissue as possible, with prolonged free drainage. Internally potassium iodide was given to the point of sat- uration. Of late he has given copper sulphate internally and uses a solu- tion of it for the daily dressing of the wounds. Ramstad (Journal-Lan- cet, Dec. 15. 1916). Cauterization with solid silver nitrate in actinomycosis of skin and soft parts in which supptiration and fistulous tracts have occurred possesses a specific action on the actinomycosis (Kottnitz). 3. Electrotechnical. — Two platinum needles, attached to the two poles of a constant-current battery, are to be in- serted into the tumor. Through the two needles a current of 50 milliam- peres is to be passed, while every min- ute some drops of a 10 per cent, iodide of potassium solution are to be injec- ted into the mass. The solution is de- composed into nascent iodine and po- tassium. This is repeated every eight days, each session lasting twenty min- utes, under an anesthetic (Gautier). Before suppuration all diseased tis- sues, glands, etc., should be removed and the parts, when possible, cauter- ized with the thermocautery. After suppuration the parts should be treated as if they were tuberculous, curetting and packing with iodoform gauze. Two cases in which actinomycosis was apparently cured by irradiation. The second patient had been oper- ated on repeatedly, undergoing about a year previously a partial resection ACTOL. ACUPUNCTURE. 321 of the upper jaw. The infiltrate dis- appeared completely under X-ray treatment alone and the fistula closed. R. Levy (Zentralbl. f. Chin, Jan. 25, 1913). Case of Heyerdahl's in which 4- eg. (% grain) of pure radium were ap- plied for 3 days to an actinomycosis beneath the right eye; there was complete cure in 2 months. H. E. Brunzel (Strahlentherap., vi, 1915). X-ray treatment especially com- bined with potassium iodide has been employed in the treatment of actino- mycosis but radium has been tried but little. The author formerly re- ported a case which was cured with radium after all other methods had failed. He has since had 5 other cases in which a prompt cure re- sulted. However, one case of actino- mycosis of the breast died of the dis- ease 4 months afterward. P. A. Heyerdahl (Trans. XI North. Surg. Congress, Goeteborg, July, 1916). A few cases were treated by the writer with the X-ray. In 1 case a beneficial action was noted; in an- other case, which is still under treat- ment, an extensive spreading of the disease resulted so that the X-ray treatment had to be discontinued. Numerous small abscesses developed which had to be incised. Rovsing (Trans. XI North. Surg. Congress, Goeteborg, July, 1916). Ernest Laplace, Philadelphia. ACTOL, or silver lactate, occurs in the form of a white powder, odorless and almost tasteless, which is soluble in 15 parts of water. Its color is changed when ex- posed to the light. Applied to the tissues, it causes coagulation of the proteids, in com- mon with the nitrate of silver. THERAPEUTICS.— Actol has marked antiseptic and disinfectant properties, ac- cording to the strength of solution used. In solutions of 1 in 500 to 200 it is used as an antiseptic for wounds. For infected wounds it may be employed as a disinfectant in stronger or even saturated solutions. But little discomfort is caused when the powdered silver lactate is applied to open surfaces. It is claimed to have a deep-seated effect by penetration to the subjacent tissues, though known to be decomposed into other com- potmds when in contact with the superficial cells. Actol has also been used internally as an antiseptic. It has been found effective in diminishing intestinal putrefaction, at the same time causing a tendency to constipation. Some have even employed it internally and hypodermically for a general antiseptic action throughout the organism. Sixteen grains (1 Gm.) have been injected subcutaneously without serious results. S. ACUPUNCTURE.— This proced- ure is principally used for the relief of tension in edematous or congested tissues. It is especially useful in edema of the scro- tum, labia, and extremities when the tissues are sufficiently distended to threaten slough- ing. Acupuncture is also employed for the relief of pain in neuritis and muscular rheu- matism, especially in sciatica and lumbago ; the benefit afforded, v.-hen such is obtained, is due mainly to reflex contraction of the blood-vessels of the area, thus reducing the congestion of the nervi nervorum and the sensory terminals to which the pain is due. In edema, the benefit is the direct result of the abstraction of considerable blood-serum imprisoned in the tissues. TECHNIQUE. — The instruments em- ployed are a very small narrow-bladed bis- toury and surgeons' needles. The part should be carefully sterilized by first washing it with soap and water and then bathing it with alco- hol or a 1 : 2000 solution of mercury. The operator's hands and instruments should like- wise be carefully sterilized. These pre- cautions are very important in view of the fact that edematous tissues are readily in- fected. If the patient is very sensitive to pain, the part may be anesthetized with ethyl chloride. For edematous tissues the small bistoury is the better instrument, one or two stabs, or, in large areas, many such, being practised, avoiding blood-vessels. A compress dipped in a warm 5 per cent, solution of boric acid is then applied to encourage escape of the serum. These must be frequently changed and the tissues kept very clean, as otherwise fetor soon appears. For muscular rheumatism, especially lum- bago, a number of round needles are thrust —21 322 ACUTE RHINITIS (SCARLETT). into the painful area from 1 to 2 inches, according to the fat overlying the part, and left in situ from five to ten minutes. The pain often ceases at once. Great care should be taken, on withdrawing the needles, not to break them, lest fragments remain in the tissues. In neuritis, sciatica, etc., the needles, several of them are tiirust into the nerve sheath at intervals (not a difficult pro- cedure in large nerve ) and left in situ about five minutes. A fine h\'podermic needle may be used, among the ordinary needles, with advantage, in the same way, and increase the efficiency of the treatment by being used to inject a little sterile water, which acts as an analgesic, or, if the pain be very severe, morphine. This treatment is efficacious in most instances where other measures have failed. S. ACUTE RHINITIS, OR ACUTE CORYZA.— DEFINI- TION.— All acute inflammatory condi- tion of the nasal mucous membrane, in which repeated attacks predispose to the extension of the inflammation to the neighboring cavities, as the pharynx ; the larynx; the lower air passages; and to a lesser degree, to the accessory sinuses of the nose. A careless sneezer and the person who does not cover his mouth and nose when he coughs are breeders of acute coryza. The organisms which cause colds are so small that a mil- lion could rest on the head of a pin. When a person coughs or sneezes, a fine spray carrying with it untold numbers of these germs is spread into the surrounding atmosphere to a distance of several feet, and may be easily taken into the mouth and nose with the respired air. More direct contact, such as by kissing, the com- mon drinking cup, the common rol- ler towel, by pipes, toys, pencils, fin- gers, food and other things which have been contaminated by the mouth and nose secretions of a per- son having a cold also carry the dis- ease. Rucker (Pacific Med. Jour., Oct., 1917). Common colds oi" tlie ordinary type are infectious. It has been demon- strated experimentally that the virus of common colds occurs in the nasal secretions; and that this virus is capable of passing through Berkefeld filters which are impermeable to ordi- nary bacteria. By the employment of special anaerobic methods the virus of common colds has been cul- tivated in vitro by the writer, and has proved capa1)le of repeated recul- tivation in sul)cultures. Experimen- tal inoculations have demonstrated that Berkefeld N filtrates of sub- cultures of the virus, in the second generation at least, are infective. Another minute micro-organism has been isolated from cultures made from filtered nasal secretions in com- mon colds. This micro-organism can be passed through Berkefeld N fil- ters, and has been recultivated from culture-filtrates. Although conclu- sive proof of its nature has not been adduced, the experiments suggest that the micro-organism descrilicd bears a definite relation to the true infective agent. Analysis of the re- sults of the writer's experiments showed that of the ten men inocu- lated, seven developed clear cut and definite symptoms of acute coryza; two reacted questionably, while one remaining case exhibited no symp- toms. G. B. Foster (Jour, of Infect. Dis., Nov., 1917). SYMPTOMATOLOGY.— The ear- liest manifestation of an acute rhinitis is a sensation of dryness or irritation in the nose, which later becomes of an itching, tickling, or stinging character. A^ery often the attack is ushered in by a preliminary chill or "a creepy feeling." Sneezing is an early symptom, and is soon followed by a sensation of fullness in the nose, with subsequent obstruction to nasal breathing, and a dull throbbing headache over the site of the accessory cavities. A general feeling of illness, with aching in the limbs and back, fre- quently prevails. The sense of smell ACUTE RHINITIS (SCARLETT). 323 and taste are interfered with. Hearing is often markedly impaired, owing to the involvement of the mucous mem- brane at the orifice of the Eustachian tube, or the extension of the inflamma- tion through the tube into the middle ear. The voice is also altered and assumes a nasal intonation. There is a noticeable loss of resonance which characterizes the normal voice, and the sounds of fft and n cannot be readily produced. The skin is dry and at times becomes hot from the presence of fever. Thirst and anorexia are also asso- ciated symptoms. The urine is scant and high colored. The existing consti- pation is usually responsible for the presence of the furred tongue. The eyelids are more or less swollen from the existing congestion, and a profuse lachrymation is not infrequently present from the extension of the inflammation through the nasolachrymal duct. The membrane of the nose is red, swollen, dry, and glazed, and is unduly sensitive. The nasal passages are practically oc- cluded by the swelling of the membrane and the erectile tissue of the turbinates to the capacity of the fossae, thereby greatly interfering with the normal physiological functions o£ the nose, as well as with that of deglutition. Owing to this existing obstruction, nursing infants at times manifest considerable difficulty in obtaining sufficient nourish- ment. The nasal discharge at first is scant, or it may be entirely absent, but it soon becomes copious, is clear, and, owing to the presence of an excessive amount of salines in its composition, it becomes very irritating to the skin of the upper lip and the nasal alse; in fact, the irri- tation not infrequently becomes so marked as to cause excoriation, or even cracking, of the bordering cutaneous surfaces. This condition, no doubt, is often very much aggravated by the frequent use of the handkerchief. As the disease progresses, the dis- charge becomes opaque, mucopurulent in character, thick and tenacious, and of a greenish-yellow color. A micro- scopic examination of the discharge shows a marked increase in the corpus- cular elements. No sharp line of demarcation exists between the second and the terminal stages of this disease. In three or four days the discharge gradually becomes thicker and scantier; the swelling of the membrane subsides ; the constitu- tional manifestations gradually lessen -and finally disappear ; the special senses assume their normal activity, and in the course of a week or ten days all traces of the disease disappear. A significant feature of acute rhinitis is the possibility of the antrum of High- more, the frontal sinus, the ethmoid or the sphenoid cells, the Eustachian tube, or the middle ear becoming the seat of disease as the result of the extension of the inflammatory process. The naso- pharynx and the pharynx invariably become involved, partly through the extension of the inflammation by con- tinuity, and partly from the interference with the normal function of the nose. DIAGNOSIS.— The recognition of this condition, as a rule, is seldom fraught with many difficulties, and the diagnosis in most cases is usually made with considerable ease. It is important, however, to guard against the possibil- ity of a mistake by making careful in- quiry into the history of the attack, and also by making a cautious examination of the nasal cavities in order to distin- guish between a simple acute catarrh and a rhinitis as the result of measles, influenza, nasal diphtheria, hereditary 324 ACUTE RHINITIS (SCARLETT). syphilis, a foreign body, a tumor, and iodism. Cases of measles and in- fluenza will invariably show a higher temperature and greater constitutional disturbances, and in the former case the appearance of the rash will elimi- nate all doubt of the cause of the exist- ing nasal condition. Nasal diphtheria can be recognized by the existence of the characteristic grayish membrane in the anterior nares and in the throat, associated with the usual constitutional symptoms. In the absence of the mem- brane, strong evidence of the condition continues to exist in tlie blood-tinged discharge, but a positive diagnosis can be obtained only by culture. The "snuffles" of hereditary syphilis is usu- ally found in very young children, with concomitant symptoms of this infec- tion, i.e., malnutrition, glandular en- largement, and in older children the characteristic Hutchinson's teeth. A foreign body or a tumor can be detected on examination, and in cases of iodism a careful history will elicit the fact that a considerable quantity of the drug has been taken. Cases of acute rhinitis are occasion- ally encountered in which the causative agent is some chemical irritant. The diagnosis should not be difficult, as con- stitutional symptoms are rarely present ; the duration of the attack is seldom, if ever, as long as the ordinary cases ; and with the withdrawal of the cause the condition invariably subsides. The patient seldom seeks treatment for acute rhinitis much before the end of the first or the beginning of the second stage of the disease, and then gives a history of exposure, quickly followed by the nasal discomfort and the rapid development of the disease. This history, in conjunction with the more or less characteristic appearance of the conditions within the nasal chambers, will usually be sufficient evidence for a positive diagnosis. ETIOLOGY.— Predisposing Causes. — If careful observation were made in each case of acute rhinitis, it would, no doubt, frequently be seen that the at- tack occurs when the resisting powers of the body are below par. Under normal conditions a certain equilibrium is maintained for the production and the elimination of the waste products of the body; but, when, for some reason, the normal function of this apparatus is interfered with and there occurs a faulty elimination of the waste products or an overproduction of the same, body resistance is lowered and susceptibility to disease becomes more marked. This condition is undoubtedly often en- couraged by indiscreet action of the patient in regard to diet, causing digest- ive disturbances, torpid liver, and con- stipation, in which the consumption of food is out of proportion to the com- bustion, thus causing an autotoxemia, in which there is sometimes a marked evidence of uric acid. It is at this time that a coryza may be considered the nasal signal of systemic poisoning, for the blood will be found tainted with the products of faulty oxidation. Strong evidence of this condition will also be found in the urine, in wdiich uric acid or mixed urates will be present. ^^*ith such lowered resistance, one becomes easily aflected by conditions such as prolonged confinement in an ill- ventilated room, extreme physical ex- haustion following overwork, or a se- vere mental strain. A lowered nerv- ous tone; interference with the normal activity of the sudoriferous glands, and the absence of a natural covering for the head, as in baldness, are oft- times important predisposing factors. ACUTE RHINITIS (SCARLETT). 325 It is not uncommon to find in some patients showing a disposition to fre- quent colds some underlying patholog- ical condition within the nose, such as deviation of the septum, a stenosis, or a hypertrophic rhinitis, thus causing the current of air to be misdirected in such a way as to act as an irritant upon a more or less sensitive membrane, which is usually below par as the result of recurrent attacks. When frequent and persistent attacks occur in childhood, a careful examina- tion of the nasopharynx will sometimes show the causal agent to be the exist- ence of adenoids. Acute rhinitis is not in- frequently found in infants under three months and those who are suffering from malnutrition, as in rachitis. It is also thought by a noted pediatrist to be a complication of dentition. In suscep- tible children, the cause is often very trivial. A curious fact exists in that this affection is seldom found in old people. An hereditary tendency seems quite apparent in some cases, notably in chil- dren. In the majority of cases, how- ever, the direct cause can be traced to an improper mode of living. The child gets very little fresh air; is confined in a room which is improperly venti- lated, usually overheated ; the windows of the bedroom are kept carefully closed at night for fear the child may catch cold; the clothing is very often in excess of what is really needed, thus making it impossible for the individual to indulge in any active play with- out producing a profuse perspiration. Under these conditions the mucous membrane, especially of the nose and throat, soon becomes very sensitive and the child is a frequent sufferer of colds Evidence sometimes points to such chronic conditions as asthma, hay fever, rheumatism, tuberculosis, and syphilis as being factors in the production of acute rhinitis. Attacks in some persons can be attributed only to their idiosyn- crasy. Excessive sexual indulgence often shows a predisposition to pro- voke an attack, as do gastric and in- testinal diseases, and a neurotic tend- ency. Thermic and climatic condi- tions are sometimes to be considered. The writer inclines to the theory of the nasal mucosas in coryza as eliminators of substances resulting^ from fauhy metabolism. Hagemann (Med. Rec, Feb., 14, 1914). Tile most potent general cause of colds in intestinal poisoning of a chronic nature, which leads to an al- teration of the vasomotor control, with the possible addition of a local cause to keep this active. Local causes ma}' be divided into two classes, malformations of the nose, and chronic disease of the frontal sinuses; then there is the cold which is simply tlie manifestation of a gen- eral condition, such as grippe. The ordinary cold in the head is most often due to bacterial infection. J. G. Dwyer (N. Y. Med. Jour., May 11, 1918). Exciting Causes. — Although certain depraved conditions of the body may be said to predispose to attacks of acute rhinitis, visually there are certain causes to which the attack may be definitely attributed. Exposure to cold and wet when the body is overheated ; exposure to sudden or extreme changes in the atmosphere ; the wetting of the feet when the system is debilitated from other diseases; or the chilling of the body from any cause, especially as the result of sitting in such a position as to allow a draft of air to strike the back of the neck or head. This seems to support tlie theory advanced by some that the impression of cold on certain parts of the body produces an inhibi- 326 ACUTE RHINITIS (SCARLETT). tory effect upon the vasomotor nerves controlling the blood supply of the nasal mucous membrane. The inhalation of certain irritating chemical fumes, such as those of iodine, chlorine, bromine and hydrochloric acid may result in a coryza. Sometimes the mere inhalation of irritating dust may produce an attack. Foreign bodies in the nose ; or certain drugs, as ipecac and the iodides, may produce the same effect. Wagner is of the opinion that the inflammation is not infrequently the result of migration of bacteria from diseased tonsils. The examination of the nasal secretion often shows the presence of a variety of micro-organ- isms, chief among which are the Micro- coccus catarrJuiUs, the Bacillus septus, the Bacillus Fricdlandcr, and the Bacil- lus segmcntosus of Cautley. The evidence seems indicative that the diphtheroids, particularly Bacillus segmcntosus of Cautley, are concerned in the production of common colds. The Micrococcus catarrhalis is much n^ore general in its manifestation, and is, probably, also epidemic and pro- ductive of a rather more severe in- flammation. It seems likely the sym- biosis of these 2 organisms increases the virulence. The pneumobacillus of Friedliindcr is much more con- cerned in chronic conditions and is probably identical with the ozena bacillus. The pneumococcus of Fran- kel flourishes in any part of the upper respiratory tract and, when virulent, has been found in pure culture. Clin- ically, the segmcntosus infection is most likely to be in the nose, seldom in the trachea, but may cause otitis media; Micrococcus catarrhalis is most apt of all to invade the larj'nx and trachea. W. Walter (Jour. Amer. Med. Assoc, Sept. 24, 1910). The writer reports having discov- ered in acute and chronic rhinitis a Gram-negative anaerobic organism {Bacillus rhinitis), which he regards as the exciting cause in at least some cases of coryza. Tunniclifife (Jour. Amer. Med. Assoc, June 28, 1913). Experiments by the writer strongly suggested that the causative virus is ultramicroscopic and filterable, the clear filtrate obtained from passage of diluted coryzal secretions through a Berkefeld N filter, and even sub- cultures from this filtrate, causing rhinitis when dropped into the nos- trils of healthy subjects. G. B. Fos- ter, Jr. (Jour. Amer. Med. Assoc, Apr. 15, 1916). The literature shows no convincing evidence that any known organism is the primary cause of the common cold. Cultural studies fail to show in uncomplicated cases any variation in the flora which would enable one to select any organisms as the cause of colds. On the other hand, where clinical complications occurred, path- ogenic organisms were definitely as- sociated with them. The writer feels, therefore, that the primary cause of colds is probably an organism as yet unknown and certainly not one of the usual pathogens such as a strepto- coccus, pneumococcus, B. influenza: or staphylococcus. But the primary cold, whatever its final cause, alters the mucous membranes in such a way as to allow secondary bacterial in- vasion and consequent frequent de- velopment of local complications. The cultures clearly indicate that such complications are due to a variety of bacteria, such as pneumococcus, strep- tococcus, and staphj'lococcus. Bloom- field (Johns Hopkins Hosp. Bull., Apr., 1921). ^^'henever the disease is at all prev- alent, suspicion arises as to the pos- sibility of it being contagious or pro- duced by some infectious material in the air. It not infrequently ushers in an attack of bronchitis, laryngitis, or one of the acute infections, such as influenza, measles, typhoid fever, small-pox. or whooping-cough. PATHOLOGY.— An acute rhinitis is characterized by the same patholog- ical changes which take place in in- ACUTE RHINITIS (SCARLETT). Z27 flammation of the mucous membrane elsewhere in the body, and may be con- sidered in three stages. Stage of Engorgement. — During this stage the mucous membrane is swollen and rather dark in color. The normal secretion at first is decreased, or even entirely arrested, and there occurs a proliferation of the epithelium. If the microscope could be used at this time, the blood-vessels would be seen to be markedly dilated and there would be more or less stasis of the blood-stream, permitting the adhesions of leucocytes to the blood-vessel walls. Their final penetration into the surrounding tissue is the beginning of the next stage. Stage of Exudation. — With the mi- gration of the leucocytes into the interstitial tissue, there is also a tran- sudation of altered blood-serum and a forcing out of erythrocytes. The dis- charge that follows is usually profuse; at first it is a mixture of mucous and serum, but this soon becomes of a mucopurulent type and finally purulent. Stage of Resolution. — This is char- acterized by the restoration of the normal function of the mucous glands, the secretion from which causes the dis- charge to become thicker and more opaque. The exudate within the mu- cosa is gradually absorbed, the lost epithelium in time is replaced by new cells, and the membrane is slowly re- duced to its normal size. PROGNOSIS.— This depends upon the severity of the attack and the extent to which the tissues are involved. The simple cases usually recover in the course of a few days to a week without any detrimental results. In some few cases, however, certain changes may take place in the tissues and increase their tendency to recurrent attacks. The prognosis becomes less favorable for an early recovery if the inflamma- tion should extend into any one of the accessory cavities of the nose and cause a suppurative process, or if there should occur an involvement of the middle ear by extension through the Eustachian tube. TREATMENT.— The treatment of acute rhinitis may be prophylactic, abortive, or curative, depending upon the cause of the attack. Persons who show a predisposition to recurrent at- tacks of coryza should guard the body against such conditions as favor their onset. The protective agencies of the body should be strengthened by regular and systematic exercise, especially in -the open air, and should be of the nature of horseback riding, golf, ten- nis, or something as vigorous. Gray- son recommends, instead of medicine, good vigorous exercise several times a day, claiming that "the quickened capillary circulation and vigorous action of the sweat glands that accompany hard exercise are incomparably more beneficial than the merely passive leak- age that follows the use of diaphoretic drugs. If in addition to this an abun- dance of water is drunk and the supply of food is greatly reduced — almost stopped in fact — we may look for an amelioration of all the coryza symp- toms in a much shorter time than if our main reliance is vested in quinine, bella- donna, and opium combinations, that have had too long a vogue." Proper discretion in diet should be practised, particularly by those who are victims of uric acid diathesis. Cold bathing, gradual at first, is an effi- cient stimulant to the relaxed vascular system. Proper selection of underwear and clothing, especially for outdoor service, should be made. If the patient is seen in the early 328 ACUTE RHINITIS (SCARLETT). stages, in the first few hours, the attack may be abbreviated, or the duration, at least lessened, if the proper treatment is immediately instituted. The patient should be given a mustard foot-bath, 4 grains of quinine, 10 grains of Dover's powder, a hot lemonade, and then put to bed with a liberal covering of bedclothes to encourage free per- spiration. This should be followed by active catharsis. The above treatment will usually necessitate the keeping of the patient in the house at least the following day. Aspirin is consider- ably used, often witli benefit. Recent investigations lead to the be- lief that the isolation of the predomi- nating organism from the nasal secre- tion and the injection into the patient of a vaccine product from the same will frequently abort an attack, and even establish a certain degree of im- munity for a short period of time. The earlier the injection, the more decided will 1)0 tlie result. A mixed bacterial vaccine is recommended by A. P. llitchens. (See Bacterial \^accines, this volume.) By means of vaccine therapy, not only arc we able to cut short an acute cold, but also to confer considerable im- munity against future attacks. By this method we can, further, often suc- cessfully treat colds which have be- come chronic, e.g., chronic rhinitis, laryngitis, bronchitis, etc. In but few cases of common cold can a stock vaccine be employed with much hope of success ; except in the case of the Bacillus septus we are not likely to do good by any vaccine other than that prepared from the patient's own person. Having secured the specimen it is forwarded to an expert, and the vaccine can be prepared ready for use within forty-eight hours of its receipt. The best time for the injection is the evening, and the best spot the flank slightly above and internal to the an- terior superior spine. If the reaction is pronounced it may be necessary to keep the patient in bed for twenty-four hours. Campbell (Practitioner, Oct., 1909). The immunity obtained lasts, on the average, from 4 to 6 months. In those subject to recurrent colds in winter an autogenous vaccine should be made from the first cold, to which may be added other stock "cold germs": staphylococcus, 400 to 800 million as the full dose; pneumococ- cus, M. catarrhalis, and M. tetragenus, of each 125 million; B, influenza, B. septus, and B. Friedlander, of each 100 million; and streptococcus, 50 million. Eight minims (0.5 c.c.) of the vaccine should contain the re- quired number of sterile germs. The vaccine is given in increasing dosage at weekly intervals until 4 to 6 doses have been administered. J. \V. Fisher (Boston Med. and Surg. Jour., June 5, 1913). The writer recommends the tak- ing of an X-ray plate of the sinuses in the headaches and neuralgia inci- dent to coryza, especially recurrent cases, and the use of autogenous vac- cines in treatment. His rule in vac- cine treatment is to begin with 3 minims of vaccine followed by 5 minims at the end of 48 hours if there is no reaction, and then grad- uallj^ to increase up to 10 minims, avoiding a reaction if possible. H. I. Filield (Med. Rec, Mar. 10, 1917). Early convalescence and the return of the normal vigor will be augmented by the administration of tonics, strych- nine and quinine being two of the favorite remedies. After two or three days this treatment is not sufficiently efiicacious and curative measures will have to be resorted to. The usual run of cases can be cured without confining the patient to the house, unless the weather is severe. In children, however, an attack which may be considered mild in an adult may be severe enough to confine the young ACUTE RHINITIS (SCARLETT). .329 patient to bed. On the first visit of a Enoug-h to cover a dime to be in- case of acute rhinitis, especially if early sufflated in each nostril, in the disease, the nasal discharge will Ointments may also be used con- be found thin and acid, and the mucous veniently by the physician, by means membrane markedly swollen. Reduc- of a flat probe. Lemoine recommends tion in the size of the turbinal bodies the following formula : — can be obtained by the application of a ^ Cocaine hydrochloride, 1 per cent, solution of cocaine and a Salol aa gr. I/3 (0.021 Gm.). 1:10,000 solution of the suprarenal Menthol gr. ss (0.032 Cm.). extract. ^^^^^ ""'^ ^^^ ^" ^"^■^" . - . J Petrolatum Bj (30 Gm.). A solution of 2 per cent, cocame and 214 per cent, antipyrin often acts to A piece the size of a large pea is greater advantage in these cases, as applied with the probe to the swollen the latter remedy prevents a violent mucosa in each nostril, reaction and frequently prolongs the Insufflations may be made w'ith : — contraction. I^ Calomel, In patients who are sufferers from Morphine hydro- gout, the cocaine will invariably fail to " chloride aa gr. % (0.01 Gm.). , ,1 1 • 1 1 *-• , ^f 4-1,0 Bismuth siibnitrate .. Siiss (10 Gm.). produce the desired reduction 01 the '- mucous membrane, but relief may be To sustain the eft'ect Ri\daux, obtained by the free administration of Grosse and le Lorier recommend the colchicum. instillation into each nostril, night and Cocaine should be used with the morning, of several drops of the fol- greatest care in infants, as they are lowing solution : — particularly susceptible to its detri- Ji Eucalyptol gr. ■f'S (0.05 Gm.). mental effects. A\'eak solutions are Sterilised liquid permissible, however, when the symp- vasehn Sj (30c.c.). toms are severe and the infant is pre- Qn the other hand, AVeitlauer. of vented from nursing. Powders contain- Innsbruck, commends the internal use ing cocaine are often prescribed for ^f sodium salicylate, combined with adults ; but it has caused cocaino- Dover's powder, wdiich, it is said, wall mania in so many cases that it should afford relief one hour after beginning only be applied by the physician him- treatment : self wdth an insufflator to cause con- „. ^ ,. ,• , . «• /-.Ar- ^ H Sodium salicylate 3j (30 Gm.). traction of the mucosa and the effect z)oz..r'.s powder gr.xlv (3Gm.). kept by means of a powder containing Spirit of peppermint... x^] (0.06 c.c). no cocaine which can be used as snuff. Tq be divided into 20 powders, 1 of which For use bv the physician the follow- is to be taken in a Httle water ever>' three or ing is efficient :— f°"^ ^^o"''^- I^ Cocaine hydrochloride, Where obstinate coryza results Camphor aa gr. j (0.065 Gm.). f'om chemical irritation ot the mu- Pulverized sugar.... 3ij(8Gm.). ^ous membranes, the writer recom- Morphine hydro- "^ends the lollowing solution:— chloride gr. j (0.065 Gm.). B Sodii siilphidi... gr. Ixxx (5.3 Gm.). Pulverized acacia, Glycerini jiiss (75 Gm.). Bismuth siibnitrate. aa 3j (4Gm.). Aqius destillata . . 3vj (25 Gm.). Pulverized uiallow... 3iss(6Gm.). M. 530 ACUTE RHINITIS (SCARLETT). The solution is used as nasal douche twice a day, one teaspoonful of it beinj^ placed in a quart (liter) of nor- mal saline solution. G. Laurens (Jour, de med. de Paris, May 3, 1916). When the profuse waterj^ discharge is very troublesome a powder con- sisting of 2 drams (8 Gm.) of bis- muth subnitrate, 1 dram (4 Gm.) of starch, Yi dram (2 Gm.) of gum arahic, with 2 drams (8 Gm.) of men- thol, or 10 grains (0.6 Gm.) of anti- pyrin may be snuffed up, and usually gives consideral)le relief. The writer has not been successful in the use of vaccines. If there is much headache or face pain an adrenalin spray of 1 to 10,000 may be employed, but this is not usually necessary. Ordinarily after the alkaline spray the following spraj' is used: B Ac'xdi carbolici. n[x (0.6 c.c). Iodine, Kalii iodidi pip aa gr. vj (0.4 Gm.) . Aquce mentli. da jss (15.0 c.c.) . Glycerini aquce q. s. ad Si'J (90.0 c.c). This is sprayed until it reaches the throat. After this an oil spray of the following composition is employed for about 10 minutes: B OJ. cloves .... tTix (0.6 c.c). Camplwmeu- thol gr. xxiv (1.5 Gnx.). 01. piiii syl- vestris ni,xx (1.2 c.c). Liq. petrolati q. s. ad .... 5iij (90.0 c.c). These measures are not expected to destroy all of the germs, but to lessen their virulence and to provide drainage. When the infection has reached the bronchi, expectorants alleviate symptoms and hasten re- covery. If the nose is treated in addition in the way outlined the pa- tient recovers in a little over half the time required when only internal medication is employed, and is able to attend to his business during the attack. T. 1". Reilly (Amer. Jour. Med. Sci., May, 1917). Aromatic spirit of ammonia and sweet spirit of niter are recommended as excellent agents to "abort" a cold by Beverley Robinson. A couple of doses of acetylsalicylic acid are also helpful. One or two doses of 1 Gm. ("15 grains) each of acetylsalicylic acid, taken at the first indication of an on- coming cold in the head, will arrest it. The drug is especially effectual when the first tickling in the throat is felt toward evening, and the drug is taken then and again in the morning. This permits him to go about his surgical tasks after breakfast without any further symptoms of coryza. If acute rhinitis has developed or the coryza relapses, two or three further doses always cured it completely. The drug probably does not act on the bacteria, but it seems to enhance the resisting powers of the tissues. Sick (Miinch. med. Woch., July 16, 1912). The writer emphasizes the remark- able power of bicarbonate of soda in arresting a "common cold." About 5/2 teaspoonful in ^^ of a tumbler of water, is repeated each half hour until 4 doses are taken. If the cold returns the same treatment causes it to cease permanently. L. Duncan Bulkley (Med. Record, Oct. 19, 1918). The administration of dionin, in >^ grain (0.03 Gm.) doses, once or twice daily, has been recommended. At home the patient should be in- structed to use one of the well-known cleansing sprays, such as Dobell's solu- tion, glycothymoline, or a solution made from Sailer's tablets. A very useful and economical solu- tion is prepared by dissolving a tea- spoonful of salt in a pint of water — practically a normal salt solution — and using it freely in the nose. In using any cleansing solution, great care should be exercised in blowing the nose directly afterward, for when it is done too harshly some of the solution mixed with the nasal secretion may be ACUTE RHINITIS (SCARLETT). 331 blown into the middle ear through the Eustachian tube and set up an inflam- mation with the formation of an abscess. Following the cleansing, the inflamed mucous membrane may be protected by an oily solution composed of : — IJ Menthol, Camphor aa gr. v (0.3 Gm.) . Liq. albolcne fSij (60c.c.). This is to be sprayed in the nose, or several drops may be placed in each nostril, and snufifed up, several times a day. If it is found impossible to drop the solution in the nose of a child, the application may have to be made by a brush. Another useful combination is : — B Menthol gr. viiss (0.5 Gm.) . Pheiiylsalicylate Sss (2.0 Gm). Boric acid 3ij (8.0 Gm.). M. fiat pulvis. Since the swelling of the mucous membranes renders the snuffing up of the powder difficult, the patient will find it advantageous to use a piece of rubber tubing about 20 cm. long; the powder is placed in it at one end, and air blown through from the other end by the mouth. An excellent agent to keep the swelling of the mucosa down is the adrenalin ointment 1 : 1000, a piece as large as a pea being applied in each nostril. During the early stage of the disease, when the nasal discharge is watery, one of the coryza tablets on the market can be used to good advantage to dry up the excessive secretion. This is particu- larly advantageous to those who are compelled to appear in public. A very satisfactory combination is the one devised and recommended by Dr. S. MacCuen Smith, which is made up as follows : — B Atropine sul- phate gr. i/goo (0.0001 Gm.) . Strychnine sulphate, Arsenous acid.aa. gr. 1^40 (0.00027 Gm.). Morphine sul- phate gr. i/ioo (0.0006 Gm.). Quinine sulphate, gr. %o (0.006 Gm.). Powd. camphor, gr. ^ (0.016 Gm.). By the time six of these are taken, at half-hour intervals, a dryness in the throat will be noticed. Only half of one should be given to a child of five years. Notwithstanding their known value among the laity, the indiscrimi- nate use of these tablets should not be encouraged, for their administration at a time when the nasal discharge has become inspissated renders the patient "much more uncomfortable and the dis- charge more difficult of expulsion. In the third stage, when the mem- brane is relaxed and the epithelium is being shed more rapidly than it should, a spray composed of 20 to 60 minims of the distilled extract of hamamelis to the ounce of water may be used to good advantage. It seems almost needless to state that the diet in all cases of acute rhinitis should be restricted at the beginning of the attack, but as convalescence takes place it can gradually be increased and finally restored to its normal status. In those cases, and especially is this true in children, where there is a tend- ency to excoriation of the upper lip and the nostril, these exposed cutaneous surfaces should be protected from* the irritating effect of the discharge by the application of vaselin or some simple ointment. Sodium salicylate causes a cold to abort if taken within twentj-four to thirty-six hours. Single dose of 7V:i grams (0.5 dram) often suffices. Taken later, it relieves symptoms and shortens attack. It is also valuable in the chronic coryza of gouty sub- 3^2 ADDISON'S DISEASE (LANGLOISI. jects. Should be taken after eating and preffsralbJy in small (doses, dis- solred in half a i: / ai- ds c. . gr- gr. J xl . : :m.i). ylx> Gn\. (180C.C— M. ThompscKD (Oh lio . State Med. Jotet^ May 1, 1919). Rurus i>. ^C-\\<.-LE-Vl . Philadelphia. ADDISON S D:SE.\SE.— In 1855. Addisc om ma' ograpb (^ vu ibe Constii..;.. ..-.. ^ j Local Effe-'- •-•'< Disea-- '' "'- '^"■^^ra- rena] Ca]'. the r. . _. een a disease kncm-n as *'bro(iized skin'' or "bronzed cachexia" and lesions of tlie adrenal bodies. The interest excited br this work at once called forth nn- merous obsen-ations on the subject, and., while a certain number of the lent support to '" 'a of c^ : j ', ia: .'aship between ■h-; *" ' ' ' . adrenals and the sj-r-' ■-■'''"•'•; ^. . . ^ ^.- son described, in , a contrary opinion was expressed- In the year succeeding the publication of his first monograph, Addison brougbt out a paper in which he described a lesion of the semilunar gang-lia unaccompanied by changes in the adrenals. We can thus state that it was Addi- son himself who originated fhe two theories which are still brought into requisition to exj^lain the manifesta- tions of the bronzed disease: the theory of adrenal insufficiency and the ner^'ous theor}\ Before discussing these hypotheses, a study of the dis- ease its.elf from the clinical aspect must first be made. SYMPTOMS. — \\'hen Trousseau proposed tliat tbe tenm "Addison's dis- ease" be applied to the affection de- scribed by tl:>e Scotch physician under the name *"broTL2ed skin," be specifically designated "'a singular cachexia espe- cially characterized by the bronzed hue assumed by the integument," "We ■^ p^efore feel n"--'"^ed in including er the term - ■ n"s disease only those affections wliich are of tlie "bronzed disease" types, and not the aggregate of all the conditions resulting from functional disturbances of the ad- renals, i-T., "without m elan odermia, no " ' '' "' r." The disease, even ■ iiiiiuc-i, MJii presents a number of ^-1 forms ^' - ■'^s: ratlier well- ; special c _ -...ristics. The -w-riter has encoimtered a nnm- bcr of cases in soldiers which would hare been classed •srith the traumatic nenroses if it v^-^-^ -t for the fact that the men pre certain symp- toms •srhich we are accustomed to er: ■ - - ise. es; -J.- w V \-l .Ana]3-sis of the cases shows a deficiency in the fnnctioniiig cf - -"s of the snprarenals. hnt i-.tit cit no manii'e?-- •■^■'- ^■^' tnber- cnlosis, no status . -5, etc The course of the afiection also is comparatirelj light and several of the men hare materially improved, while the treaad in al! is npward. Yushtchenko (iRnssky Vrada, xvi, No. 5, 1917). .- ■' '7. — ^The patieni is generally TinaL^x; iercuiosis whicij has invaded Ibese oo^gans seooodarily, tbe patient is already in the wasting stage of tuberculosis, and it is difficult to recognize the new symptoms. '\\'hcre there is primary adrenal tuberculosis, however, tbe s3Tnptomatolog\' is more AnniS(^\"s niSEASE ^laxclois). .\U characteristic. Asthenia dominates the whole picture. The least physical effort is followed by extreme lassitude. At first the patient is still capable of ener- getic and rapid muscular activity, but he is not equal to sustained work ; fatisn^ie at once appears ; later, as the process advances, lassitude becomes constant and the patient think., of but one thing — avoiding the slightest exer- tion and remaining in bed in the dorsal decubitus. The mere ingestion of food requires an eft'ort beyond the patient's strength, and the administration of solid food becomes difficult. The earliest writers had been struck by the asthenia of .Vddison's disease, and Jaccoud gave an excellent descrip- tion of it. Hut the exact conditions under which this fatigue occurs were learned through the laliors of T.anglois. Charrin, and Abelous, who explained it on the basis of a new conception of its pathogenesis. The study of nuiscular fatigue with the crgograph of Mosso permits of differentiating the resistance in an ordinary case of tuberculosis f roiu that in one of .Addisonian phthisis. The simple tuberculous subject will continue lifting the w^cight of the ergo- graph for two minutes. performiTig total work equal to 1150 grammeters; the Addisonian subject, after having lifted the weight just as energetically during the earlier contractions, becomes fatigued ver\' soon and stops exhausted before the second minute, having per- formed work equal to only 750 grain- meters. If the weight to be lifted is placed at 2 kg., fatigue already ap- pears at the fifth contraction and the sum of work done is practically nil. Melanodcrmia, or brovaing, from w^hich symptom the disease received its earliest appellation, often does not de- velop until after the asthenia. Tt ap- pears most frecjuently in the form of small, hrownisli macules scattered over the entire skin-surface, though most marked at certain points of election. The scrotum and labia majora, which are normally pig- mented, very frequently present a characteristic color. The mucous membranes are very often affected before the skin. The internal sur- faces of the cheeks, the labial com- missures, as well as the genital nuicous membranes, should always be examined in asthenic subjects. The melanodcrmia luav remain local- ized. and this is, itideed, more usually the case, but it may also become gen- eralized through confluence of the pri- •MaTy patches and involve the whole of the integiunent, making the patient's skin appear truly like that of a mulatto, though never like that of a full-blooded negro. I'rault points out that the palms and soles are not involved, but these areas are imperfectly or not at all pig- mented in negroes, and even in the anthropoid apes the soles of the feet remain of a pink color. Ca.se of .Addison's disease in a male, aged .31, in whom exposure to the sun dnrkened the picrmontation, which involved the axilla;, elbows, nipples, breast, the pubis, g-ums, lips, tongue. Of late the nails have be- come a dark brown. A. F. Chace (Post-Graduate, Feb., 101 H. The writers observed a case of Addison's disease in a boy. aged 12 years. A general bronzing of the skin (ievelope ' -radually. Tt was espe- cially marked around the nipples, the umbilicus, and pudenda. There were a number of pigmented scars on tlie body but no buccal pigmentation. The boy developed S3'nchronously loss of energy, drowsiness, a cough at night and nocturnal enuresis. The heart was small. An uncle and a brother are said to have had tuber- 334 ADDISON'S DISEASE (LANGLOIS). culosis. There were no signs of pul- monary or spinal tuberculosis and von Pirquet's reaction was negative on two occasions. The skiagraph showed calcification in the adrenal glands and discrete and dense opaci- ties at the hila of the lungs suggest- ing calcified nodules. The red-cell count was high, 6,492,000, and there was a high lymphocyte count sup- posed to be indicative of lymphatism and a bad prognosis. The eosino- philes were high, from 5 to 7 per cent. The heart was also small in this case. Rolleston and Boyd (Brit. Jour. Child. Dis., xi, 105, 1914). Traumatism of the skin is a predis- posing cause to pigmentation. The earliest melanodermic patches are often noted to appear over old cica- trices, especially over the healed areas of former blisters, and even the appli- cation of a blister or merely of a poultice on an asthenic subject is often sufficient to cause a sudden outburst of pigmentation and permit a diagnosis of Addison's disease. Gastrointestinal disturbances are fre- quent, ])ut very variable in nature. At the outset, constipation is the rule, and is accompanied by anorexia, wliich may be accounted for both by the intestinal paresis and by the general lassitude to which we have already alluded. The constipation may be succeeded, par- ticularly in the acute forms, by atonic diarrhea. But the most characteristic symptom is, without doubt, vomiting. Preliminary nausea is very seldom present ; the vomiting comes on sud- denly, and generally in the morning upon awaking. At first the patient's stomach is evacuated but once a day ; then, as the disease progresses, the vomiting becomes more frequent and occurs at intervals during the day. The act takes place with but little muscular effort, of which the subject is, indeed, incapable. The vomitus is colorless, thin, and consists of mucous. Circulatory disturbances are of great importance. The earlier observers had already pointed out a special weakness of the pulse, together with all the symptoms of cerebral anemia. The re- searches of Schafer and Oliver and of Langlois and the later investigations of the action of adrenalin served to direct the attention of clinicians to these disorders, at the same time dis- closing their pathogenesis. The Addisonian subject is in a state of hypotonicity. By reason of the ab- sence or insufficiency of the adrenal secretion, the normal tonus of the ves- sels is no longer maintained. Even at the outset of the affection, along with the first signs of asthenia, lowered arterial tension is to be found. The sphygmomanometer shows 100 to 120 mm. of mercury. The fall in pres- sure is accentuated as the disease advances; in the last stages, a tension as low as 50 mm. may be noted. Bernard and Sergent have brought out a clinical phenomenon which they claim to be useful in diagnosis without the aid of instruments of precision, viz., the "adrenal white line" — as op- posed to the red line of meningitis. To cause it to appear, the skin of the abdomen is lightly rubbed with the pulp of a finger, without scratching; after a few moments a rather broad white streak appears, which becomes more and more marked, remains stationary for three to four minutes, then grad- ually fades off. In cases showing rapid develop- ment there was an increase of urea — 2 grams or thereabouts — although the kidnej'S showed no lesions, macro- scopical or histological, at the autopsy. Sicard and Haguenau (Paris Med., May 23, 1914). ADDISON'S DISEASE (LANGLOIS). 335 Pain and Nervous Disturbances. — Lumbar and abdominal pains of great severity may be present at the outset of the disease. They frequently become localized in the epigastric and hypo- chondriac regions, and Alartineau has described a pathognomonic seat of pain at the anterior extremity of the eleventh rib. These pains, however, almost characteristic when they are sudden in onset, are sometimes entirely wanting throughout the course of the disease. When considering the pathogenesis of the affection, we shall find it easy to understand how the variations ob- served in the painful phenomena may be explained according to the extent and the seat of lesions surrounding the ^ adrenals. We have already mentioned the as- thenic manifestations, which, according to us, are referable rather to the mus- cular system than to the nervous sys- tem proper, or at leastto the structure which unites the nerve with the mus- cle— the terminal plate (as formerly designated) or the receptive substance of Langley. True paralyses are rare and in no sense characteristic. Cere- bral disturbances, such as the pros- tration, the tinnitus aurium, the hal- lucinations, and especially the en- cephalopathy of Addison's disease, may be due to two causes : cere- bral anemia resulting from vascular hypotonicity, and intoxication either through suppression of the antitoxic activity of the adrenals or through the formation of toxic products owing to functional deficiencies — asthenia, hy- potonicity, etc. General Disturbances. — The muscu- lar and vascular weakness are neces- sarily followed by disorders of a gen- eral nature. The chemical interchanges are reduced, the phenomena of assimi- lation greatly retarded, whence result marked wasting of the tissues and a strongly manifested sensation of cold generally accompanied by hypothermia. According to the view of Sajous, who considers Addison's disease as char- acterized by deficient oxidation and lowered metabolism, a study of the temperature should enable us to judge of the degree of adrenal insufficiency. The blood in cases of Addison's dis- ease presents nothing peculiar. The search for pigment in the blood-plasma has always proved negative. Gener- ally the blood-cells show diminution, but observations on this subject have been contradictory. While Laignel- Lavastine described diminutions of the corpuscles to three millions, Loeper and Crouzon found a polycy- themia. Langlois, in a comparative study of tw'o tuberculous cases pre- senting similar pulmonary lesions, but one of whom show^ed distinct Addison's disease, observed no dif- ference either in the hemoglobin percentage, the number of cells or the proportion of leucocytes. The two patients gave identical results. The secretion of urine is diminished because of the lowered tonicity. Cola- santi and Bellati, who made a study of the urine of an Addisonian patient for eighteen days, found its toxicity above that of normal urine. Langlois did not find this abnormal toxicity in the two subjects of which he made a corhpara- tive study. Course and Termination. — Addison's disease always terminates fatally, but its course may be more or less rapid. Sometimes the destruction of the adre- nals is so quickly produced that the morbid phenomena show very rapid progression. Asthenia is present al- most from the outset, the circulatory 336 ADDISON'S DISEASE (LANGLOIS). disturbances at once become very- marked, and, lastly, the gastrointes- tinal disorders, which do not appear to be closely related to the adrenal insufficiency, may become of such severity, with intractable vomiting and diarrhea, that cachexia and death supervene before the melanodermia has had time to declare itself. In the cases having a slow course, the disease may remain stationary for a long time, and it is in such cases that are sometimes observed temporary pe- riods of improvement not only with regard to the digestive tract, but also in the symptoms of melanodermia : asthenia and arterial tension. The cause of such periods of improvement it is difficult to state. Combined Addison's disease and exophthalmic goiter was observed by the writers. When the suprarenal glands are insufficient, the thyroid may come to their aid, by increasing its own functioning. In 26 cases of Addison's disease they obtained a thyroid reaction in 4. In 1 of these in this group, the thj'roid enlarged about 6 months after the visible on- set of Addison's disease. Tachycar- dia, tremor and other symptoms of exophthalmic goiter became super- posed; as they developed, the symp- toms of Addison's disease became at- tenuated. This sequence of clinical phenomena was so striking, they ac- cepted it as a suggestion for organo- therap}', and since then have been giving patients with Addison's dis- ease 0.5 Gm. (7>4 grains) of pulver- • ized suprarenal tissue and 0.01 Gm. (Yd grain) of thyroid powder in the morning, fasting for 6 days. Then they drop the thyroid, keeping on with the suprarenal treatment for 10 days and then continuing with 10 days of the 2 combined, and so on. The outcome was not very clear in some of the cases, but in 3 the im- provement was marked. Ramond and Francois (Jour. Amer. Med. Assoc, from Bull de la Soc. Med. des I16p., Nov. 16, 1917). We shall lay no stress on the mode of death by progressive cachexia, which presents nothing peculiar, but must dwell with some emphasis upon the form of death which takes place rapidly or even suddenly. The rapid fatal termination in Addi- son's disease takes on the features of an acute intoxication. The abdominal pains show marked exacerbation ; diar- rhea becomes profuse and vomiting continuous, the blood-pressure at the same time showing progressive reduc- tion. In some cases hypothermia is ob- served, with a tendency to collapse ; in others, on the contrary, there occurs hyperthermia accompanied by delir- ium and convulsions. To explain this sudden aggravation in the course of the affection, several hypotheses have been put forth. That one which appears to us the most ad- missible among them is based on a sud- den diminution, sometimes even on al- most complete suppression, of the func- tion or rather the functions of the adrenals. Almost always, indeed, such an unfavorable turn in the disease suc- ceeds upon an intercurrent infection. Now, since the researches of Charrin and Langlois, followed by those of Loeper and others, it has been known that certain infections, such as diph- theria and scarlatina, exert a selective action on the adrenal glands, causing in them a more or less marked func- tional deficiency. It is thus plain that if in a gland already the seat of tuber- culosis, but which, nevertheless, suffices to insure the adrenal function, a fresh lesion appears to destroy the surviving celkilar elements tlie symptoms of ad- renal insufficiency will show a sudden ADDISON'S DISEASE (LANGLOIS). ZZ7 outburst and be seen in all their inten- sity. Boinet has also laid stress on the appearance of serious accidents after excessive fatigue. Such occurrences confirm the investigations of Abelous and Langlois and of Albanese upon the influence of fatigue on experimentally decapsulated animals. Another theory accounts for the ag- gravating efifect of intercurrent infec- tions from the fact that, the antitoxic action of the adrenals against certain toxins no longer being exerted, the accidents due to intoxication are more severely manifested. It is evident that this hypothesis explains better' than the former the phenomena of excitation, viz., delirium, convulsions, fever. Sudden death, or at any rate death taking place within a few minutes, is not rare in the bronzed disease, and Addison had already referred to such a termination in his monograph. In 1896 Ihler was able to collect 18 cases, and since that time numerous instances have been noted. Certain cases of sud- den death in apparently healthy persons have defied explanation until the au- topsy disclosed a tuberculous or can- cerous process of the adrenals. The advent of death may be truly fulminating; a patient previously ex- hibiting no signs of aggravation in his condition may drop dead while getting out of bed or on attempting to lift a chair. The patient of Dupaigne- Beclere, who was among the first to be treated with relative success by opo- therapy, died suddenly in bed during her convalescence. In some cases the end is marked by symptoms of a more striking character, such as a sudden attack of severe vomiting, convulsions, etc. The pulse becomes frequent and thready; the face cyanosed; dyspnea develops, and death occurs. Accidental syncope, nervous shock, acute intoxication, and sudden adrenal insiifiiciency have all been advanced as hypotheses in explanation of such oc- currences. It is difficult to believe, in this connection, that adrenal insuffi- ciency can produce so rapid an effect since it is well known that completely decapsulated animals survive for fifteen to eighteen hours and show progress- ivelv increasing intensltv before death. It appears to us more reasonable to attribute the termination to nervous shock originating in the adrenal or peri- adrenal sympathetic nerves, and react- ing on the general organism with its cardiac and vascular inefficiency result- ing from decreased tonic activity on the part of the adrenals. Case of Addison's disease in a ne- gress, aged 55 years. The face and backs of the hands and fingers were intensely black — much blacker in hue than other parts of the body. The palms of the hands were also abnor- mally pigmented, but to a lesser de- gree than the face. There were nu- merous irregularly defined areas of pigmentation on the mucous mem- brane of the cheek, gums, and tongue. Her pulse was frequent, small, and regular. At the necropsy the vagina showed evidence of chronic inflammation of its mucous membrane and presented patches of pigmentation similar in character to those present in the mouth. On the vulva were a few small leucodermic areas. Both supra- renals were enlarged and exhibited caseous masses in their substance, apparently affecting the cortex. Their capsules were much thickened and adherent to the surrounding parts. They contained caseating masses, at the margin of which were giant cells, in the cortex. The condition was tubercular, with tendency to caseation. R. Seheult (Lancet, Aug. 3, 1907). Three cases of Addisonism occur- ring in the same family, in sisters, 1—22 338 ADDISON'S DISEASE (LANGLOIS). aged 9, 6, and 3J^ years, respectively. The father, mother, and an elder sis- ter, aged 19 years, were all healthy. The case of the girl aged 9 years was one of true Addison's disease. Croom (Lancet, Feb. 27, 1909). Clinical Varieties. — Several forms of Addison's disease have been described according to the relative prominence of certain symptoms. These include the gastrointestinal form, painful form, melanodermic form, and as- thenic form. These divisions are worthy of acceptance because they correspond in each case to a develop- ment and pathogenesis differing from the others. It seems probable, indeed, that in the melanodermic as well as in the painful form sympathetic changes predominate from the outset, while, in the asthenic form, adrenal insufficiency is the primary cause. According to Finkelstein, of Paris, Addison's disease in infancy is not rare, occurring in sucklings as well as in later months. Most cases are due to tuberculosis of tlie adrenals, al- though some cases have been asso- ciated with the perfectly normal glands. The most important symp- tom is pigmentation of the skin, al- though pigmentation may be brought about by a long-continued diarrhea in infants. Other symptoms are gen- eral depression and extreme weakness, diarrhea and vomiting, and convul- sions. The pulse is weak and irregu- lar. The disease is alwavs fatal, dis- solution being due to weakness, or to some intercurrent disease, especially tuberculosis. Addison's disease in children. Be- fore puberty, i.e., under 13 years, it presents considerable differences from that above this age, and is extremely rare. Analysis of 25 cases, including a personal one. As to relative fre- quency, Monti found among 200 cases 6 in children below 13, while Green- how in 330 found it four times; in other words, 1 to 62. Etiology. — The main etiological factor is tuberculosis, though the patient of Anglade and Jaquin showed no such lesion in the adrenal glands, although extensive tuberculosis in the lungs and spinal cord was present. Age: Twelve cases occurred between the ages of 10 and 13 years, 4 cases between 5 and 10, while 9 occurred below the age of 5. The youngest case on record is that of Belyayeff, of a child 7 days old. Contrarj^ to what textbooks state, that the disease oc- curs far more frequently in boys than girls, the occurrence in males and females is about equal. Family History. — Tuberculosis occur- red as a family taint in 4 cases; in one instance a rheumatic history; in one instance the mother and four children had had the disease. Previous History. — In 13 cases in which this was obtained there was tuberculosis of other organs in 3, measles in 2, scarlet fever in 2, ton- sillitis and chorea in 1. Felberbaum and Fruchthandler (N. Y. Med. Jour., Aug. 10, 1907). Hypoglycemia should be included among the symptoms of Addison's disease, as a corollary to the arterial subtension. Bernstein (Berl. klin. Woch., Oct. 2, 1911). The writer found 6 cases on record in which the right suprarenal capsule was absent; in 2 Addison's disease developed, as the other suprarenal de- veloped tuberculosis. He has recently seen a third case of aplasia of the right suprarenal. Schnyder (Schweizer med. Woch., July 14, 1921). PATHOGENESIS. — The patho- genesis of Addison's disease cannot be explained except by referring to the data of physiology, and, while Addison was deserving of high credit for pointing out the relation of the bronzed disease to changes in the adrenals, the pathogenesis none the less remained obscure because the ADDISUX'S DISEASE (LANGLOIS). 339 functions themselves of the adrenals were still unknown. Two important theories have been advanced, which, moreover, do not refer exclusively to lesions of the adrenals, but to which recourse is also had to explain the morbid syn- dromes related to lesions of all duct- less glands, including the thyroid gland, the pancreas, etc. These are : 1. The nervous theory, which at- tempts to explain all the phenomena by an action of the nervous system through its adrenal connections. 2. The glandular theory, which attrib- utes the disturbances to functional alterations in the adrenals. Nervous Theory. — The nervous theory had already been clearly stated in Addison's second paper, which pointed out the close relations exist- ing between the solar plexus, with the semilunar ganglia, and the adrenals. In France, Jaccoud became a strong partisan and defender of this theory. After him and after Addison, Haber- shon, Barlow, Schmidt, Alattei, and Martineau attributed the nervous disturbances observed to lesions of the solar plexus and semilunar gan- glia. Following Jaccoud, this view is still held by Greenhow, Jurgens, von Kahlden, Lancereaux, Raymond, and Brault. These authors offer as argu- ments, on the one hand, changes in the adrenals in cases where during life the subject had exhibited none of the symptoms referable to Addison's disease and, on the other hand, the normal condition of the adrenals in individuals declared to have Addi- son's disease before the autopsy. Jaccoud supported the theory on the basis of three orders of facts : the symptoms observed, the lesions found post mortem, and the structure of the adrenal glands. Among the symptoms observed, leaving the mel- anodermia out of consideration at once, the nervous disturbances are of two kinds : increasing asthenia and the gastric or nervous manifestations. Prof. Jaccoud, after referring to these symptoms, adds : "If we now bear in mind that in the uncomplicated cases these symptoms show progressive development in the absence of any important visceral lesion, without anemia, without albuminuria, without hemorrhage, and without diarrhea, they will without doubt appear to us as the direct and immediate result of a disturbance of the nervous system." We shall see later that these asthenic phenomena cannot be brought forth as arguments in favor of the nervous theory, and that the capsular theory, as conceived by Abelous and Lan- glois, itself finds strong support in the asthenia of Addison's disease, de- scribed by Jaccoud. The autopsy in a case of Addison's disease in a child of 10 years showed tubercular infiltration of the lungs and enlargement of the bronchial glands. The suprarenal capsules were congested, but macroscopically they presented no lesions. A microscopic examination revealed no change in the histological structure. The cap- sule was of normal thickness, and the gland, as a whole, was not enlarged. The nuclei of the cells were distinct and there was no fatty degeneration. The semilunar plexus was somewhat altered and congested. The mesen- teric glands were large, but not case- ous. Upon examination the Bacillus tuberculosis was absent. Richon (Arch, de med. des enfants, tome vi, No. 6, p. 350, 1903). In every case of true Addison's dis- ease there is a gray degeneration of the nerve-fibers of the splanchnics. This may be either protopathic, when one finds simple atrophy of the ad- 340 ADDISON'S DISEASE (LANGLOIS). renals without other inflammatory appearances in these or other organs, or (more commonly) deuteropathic, in consequence of primary disease of the adrenals or pancreas. Withing- ton (Med. News, Sept. 24, 1904). Report of a typical case in which the lesions were located in the solar plexus, the suprarenals being free from tuberculosis. Laignel-Lavastine and Porak (Bull, de la Soc. Med. des Hopitaux, July 5, 1918). The attacks of vomiting and the epigastric and lumbar pains are, in- deed, in favor of nervous lesions, and it can readily be understood how the close proximity of the sympathetic nervous structures may explain the motor and sensory disturbances ob- served in cases of bronzed disease. As for the structure of the adrenals, it does not permit of our forming any definite opinion. While it is quite true that these Sflands receive a large number of nerve-hbers from the sympathetic, as shown by the researches of Nagel, Bergmann, Kolliker, and Ilenle, there exist in the cortical layer ganglionic cells which may constitute reflex centers (Moers, Joesten, Holm) ; and while it is true that excitation of the adrenals tends to inhibit the in- testinal movements (Jacob), yet the role of the adrenal bodies cannot be denied, even on the ground of their texture alone. The main argument against the pathogenetic role of the adrenals is based on the following double series of observed facts: Mel- anodermia may exist without lesions of the adrenals ; marked lesions of the adrenals may exist without melanodermia. Glandular Theory. — The researches of Brown-Sequard, which followed the monograph of Addison at an interval of but a few months, were steeped in the idea which then pre- vailed as to the "predominance of melanodermic disturbances in the bronzed disease." P'urthermore, while unable to observe pigmentation of the skin in animals deprived of their adrenals, he pointed out the presence of numerous pigmentary granulations in the blood. The most prominent result of his researches, however, lay in the discovery of the functional importance of the adrenals, of which the role had until then escaped physi- ologists. "Death resulting from changes in these organs," wrote this author, "is preceded by a gradually developing weakness, going on to paralysis of the posterior extremities, then of the anterior, and finally of the respirator}^ muscles. Among the disorders noted may also be men- tioned anorexia, failure of digestion, rather frequently delirium, epilepti- form disturljances, and a gradual lowering of the temperature." Brown- Sequard concluded that destruction of the adrenals was followed by ac- cumulation in the blood of a toxic substance having the property of becoming transformed into pigment. Since 1855 the investigations on the adrenals have been numerous. The conclusions of Brown-Sequard have been vigorously attacked. Philip- pcaux, Gratiolet, Ilarley, Berutti, and Martin-Magron combated the vital role of the adrenals, asserting, con- trary to the belief of Brown-Sequard, that destruction of these organs did not necessarily result in death. Tizzoni, in numerous researches carried out between the years 1884 and 1889, likewise recognizes the pos- sibility of survival after destruction of both adrenals; but he points out at ADDISON'S DISEASE (LANGLOIS). 341 the same time the possibility of regen- eration of these organs when not totally destroyed ; finally he referred to medullary disorders succeeding upon destruction of one adrenal. Stirling showed that in a certain number of cases survival after de- struction of both adrenals is explained by the presence of accessory adrenals. Alezais and Arnaud ascribed the fatal ending to ascending degeneration reaching the cord by way of the splanchnics. Clinical and autopsj' findings in 3 cases: The morbid changes in the suprarenals were accompanied by corresponding changes in the other glands with an internal secretion, the thyroid, hypophysis, and spleen — all of these were hypertrophied, with evidence of hyperfunctioning. The writer does not regard Addison's dis- ease as due to a single gland, but to several participating in the process. The first sj-mptom in one patient was tremor of the arms, probably the re- sult of professional exposure to elec- tric currents, the man's work being done under an electric light of be- tween 15,000 and 20,000 candlepower. The effect of the Roentgen rays on glandular organs suggests that the light here may have affected the cer- vical sympathetic, the thyroid, and the hypophysis. Later the process seems to have extended to the abdominal sympathetic and suprarenals. In an- other case atrophy of the ovaries fol- lowed a pregnancy with premature menopause. Calcareous degeneration of the thyroid followed, with tuber- culous infection later and fulminating suprarenal symptoms. The diseased suprarenals could not obtain help from the ovaries and thyroid, and tlfere ^^as merely slight hyperfunc- tioning of the hypophysis as a de- fensive reaction. In the 3 cases patients in the last stages of Addi- son's disease recovered their energy and the bronzing subsided under thy- roid treatment. The thyroid was al- ready modified and was inadequate to supplant the diseased suprarenals, but it only required slight additional aid from without to be able to counteract temporarily the destructive process in the suprarenals. The disease, the course, the outcome, the histologic findings, the research in the experi- mental field, all sustain the assump- tion that Addison's disease, in its com- plete form, is a general affection of the entire great sympathetic system. Leonardi (Policlinico, Aug., 1909; Jour. Amer. Med. Assoc, Oct. 2, 1909). In 1891, Abelous and Langlois published their first researches on the functions of the adrenals in frogs ; these were followed bv a series of papers on the functions of the glands in other animals. They showed that, in all animals subjected to double adrenalectomy, death promptly and inevitably occurs, but that a portion of an organ if left behind is sufficient to cause survival. Muscular weak- ness and asthenia are all the more intense if the animal be forced to per- form muscular movements, whence their first conclusion "that the ad- renals possess the function of neu- tralizing or destroying toxic sub- stances evolved during muscular labor." This conception of the role of the adrenals explains a portion of the symptoms observed in Addison's disease, including the most charac- teristic symptoms : asthenia and the disastrous effects of fatigue. The discovery of the vasoconstrict- ing action of suprarenal extract by Oliver and Schafer, on the one hand, and Cybulski, on the other, that of the presence of the active substance in the blood of the capsular vein (Cy- bulski and Langlois), that of the rapid destruction of this substance in the organism (Langlois), and finally 342 ADDISON'S DISEASE (LANGLOIS). the isolation of adrenalin by Taka- mine also threw new light on the symptoms observed. The lowered vascular tension and the cerebral disorders can henceforth be inter- preted as resulting- from diminution of the tonic influence of the adrenals. The syndrome of adrenal insufficiency in its entirety can henceforth be ex- plained through the data of experi- mental physiology. Study of the nitrogen and sulphur metabolism in a patient who had Ad- dison's disease and who was on a purin-free diet. The desamidating capacity of the patient (capacity to reduce amid nitrogen) and his capac- ity to transform the sulphur of the cj'stin group into sulphuric acid were absolutely comparable to that of nor- mal individuals. A considerable de- gree of acidosis was observed, which is not accounted for by any factor which was found in this examination. The endogenous metabolism of the patient, as represented by the kreati- nin and uric acid outputs, was below that of normal subjects. Wolf and Thacher (Arch, of Int. Med., June, 1909). The writer, who had previously ob- served a striking hypoglycemia after removal of the adrenals, now reports the effect upon the glj^cogen content of the liver and muscles of the same procedure. Seven dogs were killed at intervals of four and one-half to eight hours after removal of the ad- renals. At this time all showed great muscular weakness. Their livers con- tained an average of 0.722 per cent, glycogen. If one animal be excluded, the average of the other six was 0.222 per cent. Schondorff found 18.69 to 1 .2) per cent, of glycogen in the livers of normal dogs on a similar diet. The muscle content of glycogen was 0.653 per cent., compared with Schondorff's average of 4 per cent. In three dogs dying spontaneously after operation, the livers contained no glycogen what- ever, the muscles an average of 0.187 per cent. The lack of glycogen is the cause of the hypoglycemia. The mus- cular weakness is, in all probability, due to lack of sufficient sugar and sugar-producing material, for muscle glycogen is well known to be far less readily available for the body than is the liver glycogen. Forges (Zeit. f. klin. med., Ikl. Ixx, S. 243, 1910). Adrenalin glycosuria is due to the conversion of liver glycogen into su- gar. In animals rendered glycogen- free by starvation and strychnine poi- soning, adrenalin injections cause a new formation of glycogen and sugar. Pollack (Arch. f. exper. Path. u. Phar- mak., Bd. Ixi, S. 149, 1909). Even the insufficiency or complete failure of adrenal opotherapy finds its explanation in the instability of suprarenal extracts. (We retain this vague term to convey the fact that adrenalin is but one of the principles now isolated which arc elaborated by the adrenals). But while physiology can explain and experimentally reproduce most of the symptoms of Addison's disease — those which Bernard and Sergent classify in the syndrome of pure adrenal insufficiency — she has shown herself entirely powerless to repro- duce and explain the pigmentation which is so characteristic of this affection. Excepting in one observation by Boinet, no experimenter has been able to produce pigmentation experi- mentally, either by destroying the adrenals or by setting up local irrita- tion. Following Loeper we shall refer into four groups the theories which have been advanced to explain mel- anodermia : adrenal origin, cachectic origin, nervous origin, and mixed glandular and sympathetic origin. A. Adrenal Origin. — The elabora- tion of a pigment by the secretion of ADDISON'S DISEASE (LANGLOIS). 343 the adrenals, thought of by Brown- Sequard and Pfandler, and which would be caused by lesions of the organ itself, is not supported by any evidence of value. The hemolytic function of the gland and the accumu- lation in the blood of pigment derived from hemoglobin when the glandular function is weakened are likewise too hypothetical. B. Cachectic Origin (Gubler, Teis- sier, Debove). — It is certainly true that any cachexia may provoke, along with general nutritional disorders, pigmentary phenomena. But the bronzed disease is frequently mani- fest previous to the establishment of cachexia, and presenting features , which give it a specific character which does not bear well with the general processes of the cachexia. C. Nervous Origin. — The intimate connections existing between the adrenals and the sympathetic system are such as to warrant a belief in functional changes in this system during Addison's disease. Addison had alread}^ thought of the possible role of the nervous system. Jaccoud, Lancereaux, and Raymond defended this theory. The clinical observations of Sem- mola and of Brault, who noted mel- anoderma in conjunction with sim- ple compression of the semilunar ganglia and solar plexus, and the cases of Addison's disease with lesions of but one adrenal (Green- how) are cited as favoring the view of nervous origin. Irritation of the sympathetic would presumably bring about an overproduction of pigments, either in the blood itself (von Kahl- den, Nothnagel), in the chromoblasts (Raymond) or in the cells of the epiderm.is (Behier, Chatelin). D. Mixed Origin. — Attractive as the nervous theory may be, it does not suffice in all cases, and especially is in complete disagreement with ex- perimental facts, since all excitations of the sympathetic, whether extra- or intra- capsular, have proven without efifect in producing melanodermia. A number of physicians are at present adopting the opinion of Loeper, that melanodermia is the result of changes both in the adrenals and the nervous network surrounding them. Accord- ing to Loeper, the adrenal secretion is the normal and necessary exciting agent of the nervous system in its function of regulating pigmentation. Sajous (1903) and Laignel-Lavastine hold an opposite .view : the sympa- thetic is not the regulator of pignien- togenesis, but of the adrenal gland itself, on which the formation of pigment depends. Two cases, pronounced hypoplasia of the chromaffin system, accom- panied the typical Addison's disease, while the lymph-glands were enlarged. V. Werdt (Berl. klin. Woch., Dec. 26, 1910). Case of chronic Addison's disease in a youth with the thymolymphatic temperament. The suprarenals had been totally destroyed by a primary tuberculous process, as also in a simi- lar case in a man of 41 with the status lymphaticus. Analysis of these cases and of similar ones in the literature seems to demonstrate a mutual stim- ulating action between the thyroid and the suprarenals and between the thyroid and the thymus, while there is mutual inhibiting action between the suprarenals and the thymus. Kahn (Virchow's Archiv, June, 1910). Case of male fern poisoning in latent Addison's disease. The rem- edy was given with castor oil for a tape-worm. The autops^^ showed tuberculosis of the adrenals — a true Addison's disease. Most of the cases 344 ADDISON'S DISEASE (LANGLOIS). of poisoning by male fern are those in which employment of the drug has been followed by the administration of castor oil. The use of the com- bination is strongly warned against. F. Schotten (Munch, med. Woch., Nov. 3, 1914). [I have long urged that the adrenals took part in the autoprotective functions of the body, and that when they were dis- eased poisoning occurs more readily. Hence also the vulnerability of such cases to infection. C. E. de M. S.] DIAGNOSIS.— The various symp- toms encountered in Addison's dis- ease may be divided into two groups : A. Symptoms of adrenal insufficiency. Cardiovascular disturbances ; — Lowered arterial tension. Tachy- cardia. White line on abdomen. Cerebral anemia. Syncope. Disturbances of metabolism : — Lowered temperature and sensation of cold. Progressive asthenia. Wasting. Pros- tration. Encephalopathy and various nervous disorders. Vomiting and diarrhea. B. Symptoms of irritation of the adrenal sympathetic. Melanodermia. Radiating pains. Vomiting and diarrhea. Where the Addisonian syndrome is complete and the course rapid, the diagnosis is easily made. It becomes more difficult when melanodermia is absent or doubtful. A study of the resistance to fatigue, either by means of the ergograph or by simply caus- ing the patient to perform a definite piece of work, combined with the use of the sphygmomanometer, may be of value in facilitating diagnosis, but very often in the hospital, in cachectic tuberculous subjects, the involvement of the adrenals is not discovered till the autopsy. In fact, the question of diagnosis is generally raised when it becomes necessary to attribute the melano- dermic patches to Addison's disease or, on the other hand, to some other affection producing pigmentary changes, such as the pigmentation of cachectic tuberculous cases, pigmen- tation of hepatic origin, the melano- dermias of malaria, arsenic poisoning, lead poisoning, and phthiriasis. The most common fallacy is to mis- take Addison's disease for pernicious anemia; the peculiar lemon tint of the skin in the latter condition, however, is different from that of the charac- teristic case of Addison's disease; but in slight cases confusion often arises. Fortunately, modern means of exam- ination of the blood, which in Addi- son's disease is but little abnormal, enable the recognition of the marked blood characteristics of pernicious anemia. The writer, however, advises cau- tion against being content with negativing a diagnosis of pernicious anemia because a single blood exam- ination fails to show characteristic changes. The blood in pernicious anemia varies from day to day and from hour to hour. Another possible source of confusion commonly met with, is the discolora- tion consequent on prolonged admin- istration of arsenic. By inquiry of many persons of considerable experi- ence in arsenical poisoning the writer finds that the occurrence of pigmentation in the mouth is in favor of the case being Addison's disease. In malignant disease the wasting is apt to be much more marked, and local evidence of malignancy can usually be found. Other pathological conditions some- times confounded with Addison's disease, but which ought to be easily distinguishable, are the filthy, dirty patients, infested with lice, sometimes seen in hospital out-patient depart- ments; phthisical and syphilitic pig- ADDISON'S DISEASE CLANGLOIS). 345 mentation; Hanot's cirrhosis of the liver, and bronzed diabetes. Any condition that destroys the functional activity of the medullary part of the suprarenals may cause Ad- dison's disease, by far the most com- mon being tuberculous degeneration. Calmette's reaction helps in this mat- ter. The comparative frequency of malignant disease as a cause, the au- thor considers due to the necessity of having both suprarenals affected, and, perhaps, to the fact that in malignant disease death will be occasioned be- fore the evolution of characteristic phenomena. The proportion of cases in which clinically characteristic Ad- dison's disease has failed to show dis- ease of the suprarenals is so small, about 12 per cent., as to be within the margin of allowable error due to erroneous diagnosis, inefficient post-" mortem examination, or the possibil- ity of functional disturbance of the suprarenals. Further, other glands, e.g., the internal carotid and the coc- cygeal, have cells functionally resem- bling those of the suprarenals, and it is conceivable that very rarely disease of these glands may cause Addison's disease and lead to death before the suprarenals are affected. On the other hand, when the suprarenals have been found to be diseased, and yet no Ad- dison's disease has been present, it may be that the vicarious activity of these other glands may have formed sufficient internal secretion to prevent the patient having Addison's disease. W. H. White (Clinical Journal, Mar. 18, 1908). The melanodermia of phthisical patients is all the more likely to lead one astray because of the fact that the cases of Addison's disease are almost all tuberculous. For some authors, moreover, the majority of melanodermic tuberculous cases are cases of Addison's disease in which the adrenal changes are just begin- ning-, not yet showing the signs of glandular insufficiency, but having pericapsular lesions which cause a precocious melanodermia. In pig- mented tuberculous subjects without Addison's disease the pigmentation is said to be of a lighter grade and especially the mticous membranes to be unaffected. Three cases of tuberculosis of the suprarenals in which there was no pigmentation. The diagnosis was made in two from the remarkable weakness of the patients in strong contrast to their well-nourished as- pect. Another sign is the low blood- pressure, not to be explained to any disturbances on the part of the heart. Gastrointestinal disturbances without traceable cause are further corrobora- tive testimony. These findings differ- entiate Addison's disease even with- out pigmentation of skin or mucosae. Stursberg (Miinch. med. Woch., Bd. liv, Nu. 16, 1907). Cases of liver cirrhosis and even a few incipient hepatic cases without appreciable change in the size of the liver present either disseminated he- patic patches of discoloration or a diffuse melanodermia of the same color as in Addison's disease. Here again the mucosae are but slightly or not at all involved, and the hepatic disorders place one on the right track. Arsenical pigmentation is a rare occurrence ; the same is true of sat- urnine pigmentation. In the latter the blue line on the gums is generally sufficient to permit diagnosis. In pigmentation due to arsenic, the color is more slaty in hue, and a dark mot- tling is also present, which is rather characteristic. Finally the signs of arsenical intoxication, together with the absence of those of adrenal in- sufficiency, serve to establish the diagnosis. In malarial subjects the pigmenta- tion again does not involve the mu- 346 ADDISON'S DISEASE (LANGLOIS). cous membranes, it is more diffuse and uniform, and the special indica- tions of malaria are present. The melanodermias of phthiriasic orig^in (pediculosis) seen among- vaga- bonds in a state of physiological de- bility, and who are bearers of para- sites, are accompanied by itching and cutaneous excoriations. The causa- tive agent may be discovered. On the whole, it should l^e borne in mind that the melanodermia of Addi- son's disease dififers from other forms of pigmentation in that it shows marked preference for mucous mem- branes, although this characteristic should not be put down as absolutely distinctive. Early diagnosis is all important, though often very difficult. The dis- ease gives rise to definite signs and symptoms, and usually to marked le- sions of the medulla of the suprarenal gland. The solar plexus is frequently diseased, owing to the influence of the secretion of the gland in stimulat- ing the sympathetic system. Pathog- nomonic signs are asthenia, pigmen- tation, vomiting, and attacks of faint- iiess. If these symptoms are well marked the diagnosis is not difficult, but when they have become evident the chances of successful treatment are not good. Grunbaum (Practi- tioner, Aug., 1907). Two personal cases which empha- size the resemblance existing between Addison's disease and tabes dorsalis. Both patients presented an almost identical pigmentation, and both had muscular atrophy. One was a typical case of Addison's disease, while the presence of tabes was undoubted in the other. It is not necessary to as- sume a combination of tabes dorsalis with Addison's disease, however, since other symptoms of the last-named affection were lacking. The pigmen- tation should rather be referred to tabetic changes of the nervous sys- tem. Possibly the pigmentation in Addison's disease is likewise the ex- pression of disease on the part of the nervous system. In this particular instance atrophy of the shoulder mus- cles was said to have been present ever since birth, and atrophy of the thigh muscles was claimed to have followed later, in connection with traumatism. Wagner (Berl. klin. Woch., Nu. 15, 1908). TREATMENT. — .Addison's dis- ease of pure type or manifested in the syndrome of adrenal insufficiency without melanodermia is largely caused by tuberculosis of the ad- renals. The general treatment of tuberculosis, or rather that form of treatment which is in vogue in a given locality at the time, is indi- cated. Syphilis of the adrenals is rarely diagnosticated during life; at the autopsy may be found either ex- tensive gummata, a miliary syphilo- sis or, especially in the young, a sclerosis resulting in atrophy of the gland. In doubtful cases the efifect of specific treatment may be tried. Certain cases seem to have been bene- fited by the iodides, with or without the addition of mercury (Schwytzer, A. Andrews). Cases of bona fide acute adrenitis with or without hemorrhage, which are almost always frankly infec- tious in origin (small-pox, diph- theria, etc.), generally run a very rapid course and do not possess any special line of treatment. As for the morbid growths — sarcoma, epithe- lioma, carcinoma, etc. — which it is almost impossible to diagnosticate during life, unless perhaps it be when persistent edema is noted in com- bination with the usual syndrome, surgical intervention is indicated, though the results obtained by Israel, Mayo, Kelly, Lecenne, and Hart- ADDISON'S DISEASE tLANGLOlS). 347 mann have afforded but little en- couragement. Physiological data naturally led to the trial of adrenal opotherapy. This treatment was first instituted by Abelous, Charrin, and Langlois in the form of a glycerin extract of the adrenals of guinea-pigs, dogs, and horses. The patients were in such a state of cachexia that no results were obtained, but in two less advanced cases, employing injections each rep- resenting Gm. 0.10 of the dried ex- tract, Langlois obtained better results and in particular a notable diminution of the asthenia. Since that time numerous trials have been made and the treatment mark- edly altered. Among the methods that have been tried are: 1. Hypo- dermic injections of the extract. 2. Ingestion of fresh or dried glandular substance. 3. Injection of adrenalin solution. 4. Grafting of adrenal tissue. 1. The injections of extract of the suprarenals were early abandoned because of the great pain they occa- sioned and the fact that they failed to give satisfactory results in a large number of cases. 2. The ingestion of fresh or dried gland has furnished a few unhoped- for results, together with numerous failures. Beclere and Anderodias re- port cases of cure, or, perhaps better, disappearance and long-continued ab- sence of the symptoms of adrenal insufficiency. It is advised to use the adrenals of calves and start with doses of Gm. 1.5 to 2.0, which are gradually increased to Gm. 6.0. Sajous employs the dried gland (the glandul^e suprarenales siccse of the U. S. P.). The dried extract may be given in capsules in the dose of Gm, 0.25 to 0.35 daily for ten successive days; it is left off for four days, then resumed for six to eight days, etc. Systematic testing with the sphygmo- manometer should be used as a guide in the treatment. Improvement in the arterial tone is to be considered the sign of efificiency in the treatment, while any indication of hypertonicity demands immediate stoppage of the administration of adrenal. Adams's paper in the Practitioner for October, 1903, includes an analysis of 97 cases treated with a preparation of the suprarenal glands. Of these, 7 were distinctly made worse by the treatment, 43 derived no benefit, 31 showed marked improvement, and 16 were cured. The methods in the use of glands in these cases may be divided into five heads: 1. Suprarenal grafts. Three patients were treated by this method and all died. 2. Nine pa- tients were treated by fresh glands given by the mouth ; of these, 1 be- came worse, 1 was not benefited, 6 were improved, and 1 permanently re- lieved. 3. Eleven patients were treated by hypodermic and intramus- cular injection. One became worse, 6 derived no benefit, 3 were improved, and 1 permanently benefited. 4. Sixty-one cases were treated with the fluid or solid extract of the suprarenal gland by the mouth. Of these, 2 were made worse, 32 derived no benefit, 17 were markedly improved, and 10 were permanently relieved. 5. Five pa- tients were treated by mixed meth- ods; 3 were improved and 2 cured. The cases most likely to derive bene- fit from the specific treatment are those in which the process is a chronic sclerosis and in which the other or- gans are fairly sound. D. Symmers (Med. News, Sept. 10, 1904). Series of 120 cases collected from literature, including 97 previously col- lected by E. W. Adams, in all of which adrenal preparations had been used in some form, gave the following results : 348 ADDISON'S DISEASE (LANGLOIS). 1. Cases in which death can be as- cribed to grafting or adrenal preparations 8 2. Cases in which the benefit was slight or nil 51 3. Cases in which marked improve- ment occurred 36 4. Cases in which permanent bene- fit was obtained 25 120 Analysis of these cases shows that far better resuhs could be obtained by a careful adjustment of the dosage to the actual needs of each individual case. Addison's disease being due, from the writer's viewpoint, to inadequate oxy- genation and metabolic activity, the re- sult in turn of a deficient production of the adrenal secretion, it follows that the temperature and blood-pressure in- dicate the degree to which the adrenals are still performing their functions. It is plain, therefore, that our aim should be to supply only just enough adrenal extractive to compensate for the defi- ciency of adrenal secretion produced. The 25 cases of Addison's disease in which, out of the 120 referred to above, permanent benefit occurred include one, treated by Bate, in which but M2 grain (0.005 Gm.) of adrenal extract three times daily caused very great and last- ing improvement with marked lessening of ..he bronzing. When the remedy could not be obtained temporarily, which occurred twice, the case relapsed. On the other hand. Suckling began with 10 grains daily and gradually increased until 175 grains were given each day, and also obtained favorable results. That in Bate's case the adrenals were still able almost to carry on their func- tion is self-evident, while in Suckling's the remedy practically compensated for the adrenals (while the local morbid process in them was still active, and such as to paralyze their functions — a fact \/ell shown by the severity of the case when the use of the extract was begun). The average dose is probably that used by Weigall in a very severe case — 5 grains, increased to 10 grains, of the extract three times a day. The patient increased 6 pounds in two weeks, and after about three months 56 pounds. In other words, in the 25 cases of permanent benefit, although the remedy was used empirically, it so happened in all probability that the doses employed coincided with the needs of the organism. In the 51 cases in which no benefit was obtained several occur in which failure was evidently due to inadequate dosage or to too early cessation of the treatment, while in others excessive doses — practically in every instance a too rapid or excessive increase of the dose — as clearly pre- vented a successful issue. Sajous (Monthly Cyclo., April, 1909). 3. The injection of adrenalin rec- ommended by Netter and Sergent ap- pears to us best suited for the cases showing- low arterial tension, whether of adrenal origin or not. 4. Grafting of adrenal tissue. The only rational treatment for adrenal insufficiency is grafting of the gland. Experimentation shows, indeed, that the substances secreted by the gland are very quickly destroyed in the organism, and that either the inges- tion or injection of the extract can, therefore, produce but very evanes- cent effects, whicli, besides, cannot completely replace the activities as yet unknown having their seat in the glandular cells themselves. Unfor- tunately, success in adrenal grafting is not easily obtained, and in cases where the vitality of the grafted gland has manifested itself accidents of so grave a nature have been noted that grafting has been considered an impracticable method. Courmont re- ports 3 cases of the grafting of dogs' adrenals in man and states that in all of them the results were disas- trous. His personal case developed a formidable hyperthermia and car- diac collapse. Sajous has collected from the gen- ADDISOX'S DISEASE (LAXGLOIS). 349 eral literature 120 cases of Addison's ■ I" a typical case of Addison's dis- disease treated bv opotherapy in its ^^^^ observed by the writer, the pa- various forms and presents the fol- \'^f' '''l'?^'' ^^^ ^°"\^ down from . . Ib6 to 93 pounds. Xone of the lOAMng table. remedial measures used were of the 1. Cases in which death can be ascribed least avail. He was then placed upon to grafting or adrenal preparations . 8 fresh adrenal glands from the sheep, 2. Cases in which benefit was slight or taking them raw and minced. As he w'^ 51 developed repugnance to these desic- 3. Cases in which marked improvement cated gland was substituted. The occurred 36 improvement was striking, all the 4. Cases in which permanent benefit was symptoms showing change for the obtained 25 better. He had recovered 50 pounds J20 of liis weight, and his improvement In a typical case reported by the otherwise was harmonious, when writer in a woman of 33 years, ad- suddenly and without apparent cause renal gland, tuberculin every 10 days, ^^"*^ gastritis set in, with prostra- and iron and arsenic, caused im- *'°"- ^* '^'^^ ^°""^ ^^at he had sus- provement, the blood-pressure rising pended his adrenal treatment for from 95 to 110. In 6 weeks the pa- °''" ^ ''■^^'^'^- ^'^ stomach was un- tient was very well, and went to the ^^^^ *° '■^^^'" anything. Cerebral country. She soon relapsed, however, symptoms now set in and death took and the treatment was repeated with P^^^^ ^''^'^ ^°™^- ^^^ ^^^^^^ ^^ ^^'^ no good effect. During a period in ^^^^ '^ ^''^* ""'^ ^'^''^ "°* sufficiently which she was very weak and low, *^^^^^ organotherapy in these cases. transplantation of an adrenal was ^^^^'" <^°^"*- "'^^^ ^^'o^h., Aug. 1-8, performed. On March 17th a male 191_). patient died of heart disease. The ^^^^ Addison's disease can often be cadaver was taken immediately to benefited, and sometimes even recov- the anesthetising room adjoining the ^''^^ ^'■°™' ^* ^^""^^ ^" '^^ glandular operating theater, and the right ad- manitestations (its most important renal removed and placed in normal °"^^^ ^>' adrenal opotherapy, which saline solution at 100° F. In the op- "°* °"^>' ^^^^^ "P for deficiency of erating theater cocaine and adrenalin secretion, but also leads to a com- solution w^as infiltrated over the pensatory hypertrophy which to lower ends of the patient's recti ab- ^°"^^ ^"''^^"t replaces lost glandular dominis. A longitudinal incision was *'^^"^- Sergent (Jour, de Med. et de made on each side, and the sheaths ^^"■- ^""^^^ J""^ ^^' l^^^^" of both right and left recti laid open. ^^ typical case of Addison's disease The adrenal was bisected, and half of '" ^^-' ^"^^^ ^^'^'^ adrenal gland, left the gland was then buried in each ^^ °"'>' symptom a discrete melano- rectus muscle. The sheaths of the dermia. Eleven years later the pa- recti were then closed with contin- *'^"t ^'^^ °* -^^^"^ cancer. The uous catgut sutures, and the skin autopsy showed a small cicatrix in wounds with horse hair. The patient *^^ ^^" adrenal. Hirtz and Debre was very ill after the operation, but ^^^"^ ^^^^•' J""^ 27, 1914). from 21st March improved rapidly. In a case of advanced Addison's By 2d April she was up. and was at disease observed by the writer, an the time of writing in comparatively intravenous injection of adrenalin good health. The pigmentation was caused sweating over the entire body distinctl}- less, and she had gained and then sudden arrest of both the one stone (14 pounds) in weight. heart and the respiration. Only after The blood-pressure on the 19th June half an hour's vigorous artificial was 104. D. Murray Morton (Aus- respiration was the patient revived, tral. Med. Jour., July 6. 1912). In another case an intravenous injec- 350 ADENITIS (WITHERSTINE). tion was followed by intense tremor and pallor, and the left side of the face alone was bedewed with sweat. Lowry (Med. Klinik, Nov. 1, 1914). Exceptional cases as regards the extreme tolerance of the patient for epinephrin. The man of 38 with grave symptoms of suprarenal in- sufficiency was given 10.5 mg. {Vi grain) epinephrin in four and a half hours; this included 2 mg. (Y.-.-i grain) subcutancously and 8.5 mg. (% grain) intravenously. No sugar appeared in the urine and the blood-pressure was not brought up quite to the normal figure even with this. The following days 6 and 4 mg. ('/io and Mo grain) were given. There were no signs of intolerance at any time, even though to attain the desired therapeutic re- sult these large doses were found necessary. The case teaches that we need not shrink from large doses of epinephrin in emergencies, as with acute suprarenal insufficiency under chloroform, or with gaseous gangrene or other hypotony of infectious origin. By watching over the blood- pressure as the epinephrin is being taken, we can continue it and push it until the arterial pressure is brought up to a point where the functioning of the organs is possible once more. Nolf and Fredcricq (Arch. Med. Bei- ges, Aug., 1917). Two cases treated by the writer retrogressed even to the pigmenta- tion of the mucous membranes under tonics and systematic administration of suprarenal gland. The patients were men of 65 and 70 who had been subjected to great privations. The suprarenal deficiency had evidently been merely functional. Quincke (Therap. Halbmonatshefte, Jan. 15, 1920). If tuberculosis is suspected the treatment of this condition should also, according to Sajous, be resorted to. In a case observed by the writer suspected of tuberculous origin, the patient's sister having died of tuber- culosis, the patient was treated in the usual climatic and general hy- gienic way, and in addition received several courses of tuberculin injec- tions. The patient is in good health and able to perform rather arduous duties. Munro (Brit. Med. Jour., Mar. 23, 1912). [The administration of adrenal gland alone often fails to cure. In truth, adrenal gland should be regarded only as an im- portant adjunct to the treatment of the causative disorder, and an agency calcu- lated to compensate for the reduced secre- tion the diseased adrenals produce. C. E, UE M. S.] J. P. Langlois, Paris. ADENTIIS. —DEFINITION.— Tnllainniation of a gland. VARIETIES.— Adenitis may be acute, due almost invariably to infection from an attack of angioleucitis and oc- casionally to injury or strains; or chronic, resulting- from either of the preceding, especially in strumous or cachectic persons, and frotn slight sources of irritation, and not uncom- monly resulting in permanent enlarge- ment and induration or in tuberculous degeneration. Adenitis of specific ori- gin will be described under Syphilis and Urin.vry Sy.stkm. ACUTE ADENITIS. SYMPTOMS.— The general symp- toms depend upon the extent and severity of the infection. Rigors may occur when pus forms. The tempera- ture is frequently elevated. If the in- fection is severe, symptoms of pro- found septicemia appear. The local symptoms are, by far, the most prominent in the majority of cases, and consist of pain, heat, and sw^elling. The suffering varies from a slight sore- ness only to intense pain according to the position of the gland, its relations with the surrounding tissues, and the ADENITIS (WITllERSTINE). 351 density of tlie tissue in which it is im- bedded. The heat may vary according to the degree of the congestion present. The swelhng may either be great or sHght. If the lesion be confined to the gland, it will be well defined ; if peri- adenitis is present, the swelling will be more or less dift'use. Glands in any re- gion of the body may be afifected, but those of the neck, axilla, and groin more than the others ; this is due to the fact that infection generally enters the system through the mouth, throat, genital organs, and the extremities. In the congestive, or exudative, stage, pain and swelling are present in the region of the glands ; if the glands are superficial the swelling is ovoid, with the long axis coinciding with the direc- tion of the afiferent lymphatics, and pal- pation reveals several movable, hard, elastic, and tender rounded masses. When the glands are deep, as in the axilla, abdomen, or even the neck, the results of palpation are less definite and unsatisfactory. In the suppurative stage the pain in- creases and becomes sharp and catch- ing, the skin reddens, and the periglan- dular tissue swells. If the gland alone suppurates, the skin remains normal, while under it may be felt the softened and enlarged gland. This latter opens outwardly or into the neighboring cellular tissue on from the sixth to the fifteenth day of the afifection. \\'hen the gland opens outwardly, the cicatrix is much smaller than when it ruptures into the cellular tissue, as in the latter case it gives rise , to an abscess. If the cellular tissue around the gland suppurates, the skin becomes quite hot, swollen, and painful, and fluctua- tion may be felt. Two foci of suppu- ration are thus established. The skin is occasionally undermined by the pus. Recovery is possible, however, w^ithout suppuration of the gland. Both the gland and the cellular tissue around it may suppurate, either simul- taneously, or suppuration of the cellular tissue may precede that of the glands, or the latter may suppurate and rupture into the surrounding cellular tissue and form an abscess. Pus is usually pro- duced in considerable quantity, and the affection is of long duration. Suppurative adenitis may result in cicatrization after several weeks. This cicatrix may reopen to allow the exit of pus from a suppurated gland. On the other hand, a fistula may result, which may give exit to seropus or to lymph (Despres). A lymphatic gland or vessel will then be found at the bottom of the abscess cavity, below the crater- like opening. As the suppuration usually starts in more than one focus in the gland, the first sensation to the touch w'ill be one of bogginess, which periglandular con- gestion may render obscure. Well- defined fluctuation is found only when considerable tissue is destroyed. Two cases of adenitis of the elbow due to fever were observed by the writer. In the one case staphylococci were found in the pus evacuated from the epitrochlear lymph-node in a con- valescing young child. The germs may have entered by a small wound of the thumb. In the second case of the same kind the epitrochlear lymphadenitis subsided without sup- puration under systematic application of wet compresses. It was probably a primary tj^phoid lesion. L. Ver- delet (Jour, de Med. de Bordeaux, Apr. 21, 1912). DIAGNOSIS.— The diagnosis of ordinary superficial acute adenitis is usually easy ; it is more difficult when the neighboring cellular tissue is also 352 ADExMITlS (WlTHEkSTlNE). inflamed ; it may be im|)o.ssiblc in cases of deep-seated or visceral adenitis. In adenitis of the inguinocrural re- gion the swelhng is found in the ex- ternal portion of the region if due to a lesion of the gluteal tissues, and in the inner portion of the region if due to a lesion of the anus, perineum, or external genitals. In both conditions the tumor will have its long axis directed more or less horizontally. The swelling will be found in the lower portion of the inguinocrural re- gion, with the long axis directed more or less vertically, if the lesion causing it is situated on the foot, leg, or lower part of the thigh. This disposition is due to the anatomical relations of the lymphatic vessels and glands, and should be borne in mind. Operation for strangulated crural (femoral) hernia has been performed for an adenophlegmon of the crural canal. Supraclavicular adenitis, while fre- quent in phthisis, is not present in every case. Yet it is of great diagnostic value when present. There may be a few or a great number of slightly enlarged glands, and they are frequently bilat- eral. The cervical glands may also be enlarged. There is no pain, nor does the swelling increase, remaining just the same for years. They rarely ac- company apical tuberculosis, but are generally found with peripheral, sub- pleural lesions. The writer considers that the presence of enlarged supra- clavicular glands confirms the diagnosis of doubtful phthisis. C. Sabourin (Jour, des praticiens, Dec. 27, 1902). New sign described, based on aus- cultation at level of seventh cervical or first dorsal vertebra. When the child speaks in a low voice the voice sound is accompanied by an added whispering sound, localized to one or two vertebrje, or extending even to fourth or fifth dorsal vertebra. It is present long before dullness appears. The bronchial quality of respiration over this area is also significant, but it only appears when the glands are considerably enlarged. The absence of abnormal breath sounds and apical rales affords corroborative evidence. D'Espine (Brit. Med. Jour., Oct. 15, 1910). ETIOLOGY.— The lymphatic glands serve as reservoirs on the course of the lymphatic vessels, through which any irritants or infection must pass. Glandular enlargement indicates an infective process situated in the lymph tissue specifically drained by such "glands. In most cases of acute associated infection the glandular en- largement subsides as soon as the infective process is removed. When chronic cervical glandular enlarge- ment persists in spite of local treat- ment of the throat the lymph tissue involved — the tonsils — is frequently the seat of a tuberculous lesion, the glands being secondarily infected. E. B. Gunson (Brit. Jour. Child. Dis., Oct.-Dec, 1917). Cold and overexertion act as local depressants, and thus may indirectly favor the development of adenitis. Gen- eral debility has the same efTect. The following varieties of adenitis, etiolog- ically regarded, are recognized : — 1. Adenitis by contiguity, resulting from the propagation, by contact, of a neighboring inflammation. 2. Adenitis by continuity or follow- ing lymphangitis. 3. Adenitis by embolism, due to the transportation of septic or irritating matter, produced in the system or com- ing from the outside. Adenitis of the mesenteric glands may be due to dysentery or to the inflammation of Peyer's patches in typhoid fever. Adenitis occurs in carbuncle, furun- cle, vaccination, erysipelas, and eruptive or infectious fevers. Attention has been called by many ADENITIS (WITHERSTINE). 353 observers to the frequent association of enlargement of the cervical glands and diseased tonsils. So often has this been found that every patient suffer- ing- from cervical adenitis should have the tonsils examined, with a view to their removal if diseased. The con- tents of the tonsillar crypts should be examined microscopically, and the identity of the bacterial growths therein ascertained. It is wise to sub- mit the tonsillar mass to bactericidal measures — e.g., iodine in glycerin — some time before removing them. The writer made histological ex- aminations of 65 whole tonsils re- moved from children; 57 tonsils of patients not clinically tuberculous showed no tuberculous lesions. Of eight patients with tuberculous cervi- cal adenitis the tonsils were found tu- berculous in 5. F. S. Matthews (An- nals of Surg., Dec, 1910). A child with enlarged tonsils and adenoids is not ill because of the in- creased size, but because of a chronic infection of its faucial and post-nasal lymphoid tissue, which serves not only as a nidus for the manufacture of toxins, but also as a port of entry for many other systemic diseases. This condition of chronic infection, which is extremely common, is easy to diagnose if the 3 cardinal physical signs — enlarged tonsils, rhinitis, and enlarged cervical glands — are kept in mind. Running ears, bronchitis, mas- toiditis, etc., are phj'sical signs to be noted, more correctly described as complications. The disease is highly infectious, as shown bj^ the facts: (1) That it is far more frequent among school children than among children who do not go to school; (2) that when one child in a family is attacked the disease subsequently spreads to others who were previ- ously healthy; (3) micro-organisms can always be grown from the nasal and post-nasal secretions, which are normally sterile. There is a tendency to chronicity, the child in such case 1—23 being a "carrier" and consequently a source of danger to other children. P. W. Leathart (Brit. Med. Jour., Feb. 14, 1920). PATHOLOGY. —If suppuration does not occur, resolution may take place, or chronic enlargement of the gland may follow hyperplasia of the connective-tissue stroma of the gland. If suppuration does occur the sur- rounding connective tissue may, and usually does, suppurate ; then the more or less disintegrated gland lies in a suppurating cavity formed by the circumjacent connective tissue. ' There are two forms of acute ade- nitis, depending upon the degree of inflammation present: — 1. Exudative adenitis. In this form the gland is swollen, and it feels hard and elastic. On section it appears red- dish brown, like the spleen, with small foci of hemorrhage, all of which indi- cate excessive dilatation of the capil- laries. The lymphatic stream is ar- rested by the dilatation of the cortical lymph-sinuses and their obstruction by fibrin, granular material, and por- tions of altered white corpuscles. The lymph-follicles are filled with fibrin and accuriiulated lymph-cells. The stroma of the gland is swollen and infiltrated with cells. If the section of the gland is scraped, a milky liquid will be ob- tained, which contains white corpus- cles and epithelial cells, the latter showing several nuclei. 2. Suppurative adenitis. In this va- riety the gland softens, its tissues be- come more brittle, hemorrhagic infil- tration centers form that soon change into yellow, purulent foci. These, at first distinctly separate, soon unite, forming an abscess within the fibrous capsule of the gland. Sometimes the 354 ADENITIS (WITHERSTINE). periglandular tissue suppurates, while the gland does not. The glandular abscess and the peri- glandular abscess may open externally, each one separately or both simulta- neously. The suppurating gland may rupture into the cellular tissue. Occa- sionally the gland is hard and elastic ; it may be difficult to separate it from its fibrous capsule. The afferent lym- phatics are enlarged and thickened. The lymph-cells and cortical follicles are few in number and have under- gone grannlofatty degeneration. PROGNOSIS.— The prognosis is usually favorable; it may be unfavor- able, however, when extensive abscesses form in the neighborhood of important organs. Deep-seated suppurative adenitis may give rise to dangerous complications, especially in certain regions, like the neck and mediastinum, on account of the purulent extensions (through bur- rowing) and the difficulty of evacuating the pus. Ulceration of the great vessels of the neck giving rise to grave hemorrhages may also occur. TREATMENT.— The first indica- tion in acute adenitis is to remove any source of irritation or infection. Any wound, abrasion, opening, or any natural cavity with which either of these may connect should be so treated as to bring about absolute local asepsis. Enlarged glands of the neck are not, primarily, tubercular, and bear the slightest relation, if any, to general or pulmonary tuberculosis. They are due to a mixed infection of pus-producing bacilli, and will quickly resolve if the source of the infection is removed be- fore the glandular tissue becomes dis- organized. If di.'^organization takes place, the gland should be poulticed unt'I it is practically liquefied. Tt shoi'.IJ then be opened by a stab puncture, emp- tied and drained by a Briggs cannula. Cases seen late with a large mass of partially calcified and partially disor- ganized glands present call for a thor- ough and extensive dissection. Treat- meni, other than local, should be food, fresh air, and proper clothing. F. D. Donoghue (Boston Med. and Surg. Jour., Mar. 28, 1907) . The region in which the affected gland is situated should be kept at rest and, if possible, elevated. In this man- ner the afferent arterial current is diminished, while the efferent venous and lymphatic currents are increased. To prevent suppuration, gray mer- curial ointment, very gently rubbed in, is useful. The injections of from 5 to 10 minims of a 3 per cent, carbolic acid solution into an inflamed gland have also proven satisfactory. If it is desired to hasten suppuration, warm antiseptic fomentations are to be used in preference to poultices. The compound resin cerate of the pharma- copccia,is effective for this purpose, and is antiseptic as well. \\'hen pus has formed, the gland should be opened by a generous inci- sion, sinuses, if present, being opened throughout their entire Icngtli to facili- tate treatment. The contents are then carefully removed, and the infiltrated wall scraped with a sharp curette. The cavity should then be packed with iodo- form gauze, or gauze impregnated with camphorated naphthol or salol. The dressing may be removed on the third day. In addition to climatic and general tonic treatment, the writer advised the evacuation by puncture of suppurative ac'enitic. and the injection of a mixture of iodoform, 1 part: ether, 10 parts; oil of sweet almonds, 109 parts; creo- sote. 2 parts. In chronic cases cure may be obtained in two or three months after about twenty punctures. Robin (Tribun- med., xli, 249 1908). ADEXmS (VVLTHERSTINE). 355 Balsam of Peru is a valuable curative agent, as it is not only antiseptic, but is a stimulant to healthy granulation. It is applied directly to the open, cleansed wound, and then covered with gauze and retaining bandage. In the treatment of cases of simple chronic adenitis, applications of iodine, compression, and local blistering have given the best results. Blisters, nitrate of silver, or iodine tincture should be applied around, but not over, the inflamed gland. Excision may be performed if the mass be large or disfiguring. In cervical adenitis due to tonsillar infection some authors have strongly advised the thorough removal of the diseased tonsil before attempting the external operation upon the glands, especially in those cases in which the lymph-glands have not broken down. The extension of the infection through the lymphatics from the tonsils is thus checked. The writer emphasizes the import- ance of radiographic study in all cases of cervical, facial, and submaxil- lary adenitis. The external appearance of the teeth does not constitute reliable evi- condition. The cooperation of the dental sur- geon is indicated for the successful and expeditious treatment of sub- maxillary, cervical, and facial ab- scesses which have their origin in dental and peridental infections. B. Lipshutz (N. Y. Med. Jour., Mar. 16, 1921). Electricity, preferably the constant current, is highly recommended by some authors. Daily sittings of ten minutes each, using 5 to 15 milliaiuperes, are required. Codliver oil, the iodides, and iron are indicated in all cases when the digestive organs do not rebel against their use. Arsenic and strychnine are the agents next in order, and sometimes prove very effective. Out-of-door life and plentiful nourishment are of pri- mary importance. The writer em.phasizes the impor- tance of the relations between the glands in the face and neck and the teeth, tracing the development of in- fectious processes including adenitis, to the teeth, especially in children. Vaccine therapy is extolled when the adenitis is once established. If the eflfect of the vaccine in a few hours is slight or transient, the presence of pus is indicated and requires elimi- nation before the vaccine can exert its efficacy. The focus must be drained continuouslj-. He prefers for this a loop of fine copper wire, such as is used for electric light, the outer ends turned back, and the whole held in place with a strip of gauze. This loop can be inserted and removed without inconvenience through a minute incision. He prescribes flush- ing with an antisepti-c unless the cav- ity be sufficient to permit the use of the Carrel method. Even when the adenitis is only indirectly connected with the mouth, the vaccine made • from the inouth germs still shows efficac3\ Landete (Arch. Espan. de Pediat., Aug., 1918). CHRONIC ADENITIS. SYMPTOMS.— The symptoms vary according to the period of development in which the diseased gland is found at the time of examination. Three periods of development are commonly recognized in tuberculous adenitis : the period of induration, or indolence ; the period of inflammation, and the period of suppuration. 1. Period of Induration, or Indo- lence.— This period may last for years, and resolution may even take place, though the gland always remains some- what enlarged and indurated. The gland.; are felt as hard, elastic, enlarged 356 ADENITIS (WITIIERSTINE). bodies, rolling under the finger, witli more or less distinctness as they are situated superficially or deep. No heat, pain, or redness of the skin is perceived. 2. Period of Inflammation. — In this period we have pain, redness of the skin, and tenderness on pressure. The gland, if solitary, may adhere to the skin. Fluctuation may be present. 3. Period of Suppuration. — In this period we notice much more softening of the contents of the gland than a real suppuration. The skin may ulcerate through almost without inflammatory symptoms, and the contents — consisting of caseous matter half-dissolved in a whitish watery fluid — may be evacuated. When ])eriadenitis occurs, true pus may be present. If chains of glands are tuberculous, the latter inflame alternately and dis- charge their contents in the same order, a series of abscesses being thus formed. When the contents of the gland are discharged, the skin may become ulcer- ated in the neighborhood, form fistulae, and after healing leave a depressed, adherent, violet-colored cicatrix. In some cases a fistula may form and last for years ; the skin may be under- mined, and disfiguring cicatrices may be formed. Cretaceous transformation occurs at times in the deej^er glands, but rarely in the superficial, ones. Some caseous glands undergo a process which trans- forms them into a cyst-like cavity con- taining a serous liquid. In chronic adenitis the glands may become painful by the compression of small nerves, or of neighboring organs ; when they are inflamed a small, hard mass usually appears, either alone or united with others, which may become enlarged and suppurate, or persist with practically no change for years, or finally disappear if the cause of irrita- tion be removed. Chronic adenitis may assume various forms. 1. Geneial Tuberculous Adenitis. — This presents itself especially in ne- groes. Organs other than the glands are but little aff^ected, and continuous fever exists. The retroperitoneal, bron- chial, and mesenteric glands are the most enlarged. It resembles in many ways an acute attack of Hodgkin's disease. As long shown by Grancher and jMarinescu, the majority of children j)resenting symptoms of tuberculosis also have general adenitis, the swollen glands being felt everywhere ; they never change in size or consistence. Suddenly a bronchitis develops, fol- lowed by a bronchopneumonia, from which the child dies. Microscopical examination reveals caseous spots and the presence of tubercle bacilli throughout the affected glands. Cases of cervical adenitis are usu- ally supposed to be tuberculous, yet, according to the writer some may be gummatous, and careful study should be made to prove or disprove this supposition defmitely. The clinician should ol)tain an exhaustive history of each case to jrrive at a correct diagnosis. Coues (Boston Med. and Surg. Jour., Nov. 18, 1915). To the familiar relation between the teeth and the cervical glands the writer also adds a mechanical factor — the pumping into adjacent tissues of debris through loose teeth and mastication, an open door for the entrance to the glands of tubercle bacilli. G. H. Wright (Boston Med. and Surg. Jour., Jan. 7, 1915). In the majority of cases (80 per cent.) of clironic cervical adenitis, where no obvious source of infection is present, the tonsils are infected. The size of the tonsil makes no dif- ference as to their infectivity, except ADENITIS (WITHERSTINE;. 357 that the small tibrotic variety is likely to be more dangerous than the large. The organisms are present in the deepest parts of the gland. Gardiner (Lancet, Oct. 2, 1915). The tonsils which are drained by their lymphatics into the cervical glands frequently contain tubercle bacilli. These may penetrate the ton- sillar membrane without leaving any mark. In 50 per cent, of cases of tuberculous lymphadenitis, the ton- sils are also infected. Hence the ton- sil is an important portal for entry of the tubercle bacilli into the human organism. W. B. Metcalf (Jour. Ophthal. and Oto-Laryn., xi, 71, 1917). [As I have emphasized in the article on the Thymus and Lymphatics (in the eighth volume) the lymphatic nodes are not mere barriers for bacteria, but protective structures in which all kinds of pathologic organisms are assailed by phagocytic lym- phocytes, in order to stay as long as pos- sible, and perhaps prevent, their penetra- tion toward the blood-stream. While a proportion of enlarged lymphatic glands are tuberculous, others may be due to the presence in them of other organisms, a fact which imposes the necessity in all cases of ascertaining the causative agent among the many now recognized. The foregoing abstracts illustrate this fact. C. E. deM. S.] 2. Local Tuberculous Adenitis. — (a) Cervical. This form is usually met with in children, and begins in the submaxillary glands, which are gener- ally more enlarged on one side. In a study of glands secured from 110 cases of cervical adenitis, and ex- amined directly and by culture and inoculation, the writer found that of these, 10 sets of glands that were not tuberculous macroscopically, failed to produce infection in guinea-pigs. Glands from 29 other cases, all mac- roscopically tuberculous, and 15 of which showed bacilli on direct ex- amination, all failed to infect guinea- pigs, the bacilli being no longer active. Glands from 71 cases pro- duced tuberculosis in guinea-pigs. Of these, Zl contained bacilli of the human type and the 34 remaining of bovine type. Analysis of the relative frequency of the 2 forms of infection at differ- ent age periods showed that the pro- portion of bovine infections was greatest in children under 5 years of age (90 per cent.), but that the bovine type of organism was by no means rare in adults over 20 years of age (23.5 per cent.). A. S. Griffith (Lancet, June 19, 1915). (&) Bronchial. This form is thought to be always secondary to a focus in the lungs, by some authors, but this opinion is contested by many others, Osier among them. Local lung infection, pericardial infection, and general infec- tion are to be feared, however. (c) Peribronchial. In this form we must realize the importance of lesions resulting from caseation. There is a softening of the lymphatic glands situ- ated around the lower end of the trachea and main bronchi. Evidence from percussion is of doubtful value ; alterations in breath-sounds are much more important, especially when uni- lateral ; divided respiration, with pro- longed expiration, is found unaccom- panied by any adventitious sounds. In cases in which the enlarged glands ulcerate through the air-tubes, the breath has a very offensive odor, and coexistence of fetor with hemoptysis and evidence of pulmonary consolida- tion is suggestive. When vomiting of blood and its passage by the bowel are added, the diagnosis of glands ruptur- ing into the bronchus and esophagus is the most likely one. General tuberculous adenitis is likely to occur in such cases unless prompt treatment is instituted. ((/) Mesenteric. This form may be primary, and is thus very common in 358 ADENITIS (WITHERSTINE). children, or secondary to local intest- inal tuberculosis. The sufferers are usually weak and wasted ; the abdo- men is enlarged and tympanitic, and diarrhea is a common symptom. Some fever is usually present. This form may exist in adults. Sims Woodhead found tuberculous mesenteric glands in 78.7 per cent, of necropsies on tuberculous children, and in 11 per cent, the mesenteric was the only lesion present. Colman found them in 66 per cent, of the necrop- sies; Walter Carr in 54 per cent.; W. P. S. Branson in 22 per cent. When this condition exists in adults, it affects oftenest the glands of the appendi.x or of the ileocecal region because, according to Corner: 1. The cecum is like the stomach, a resting place for the bowel content. 2. The bowel contains a maximum number of organisms in the cecum. 3. The lymphoid tissue has its greatest development in the ileum, the cecum, and especially the appendix. Louis Rassieur (Jour. Missouri State Med. Assoc, Feb., 1909). The recognition of thoracic tuber- culous adenitis in young children is at times very difficult. In 2 instances in infants studied by the writer, the symptoms from mediastinal glands included dyspnea suggesting asthma. Laryngospasm occurred. Cough was the most constant symptom — a spas- modic, dry cough, resembling that of whooping cough. Martagao (Bra- zil-Medico., Feb. 28, 1920). The tracheobronchial glands are divided into 2 groups. The first or pretracheobronchial group lies in 2 parts alongside the trachea and in the superior angle formed by the trachea and the large bronchi. The second or intertracheobronchial group lies in the inferior angle formed by the bi- furcation of the trachea. Clinical phj'sical signs of enlargement of these glands are Smith's sign or venous hum over the manubrium of the ster- num with the head in forced exten- sion; D'Esf'iiic's sign of bronchophony or pectoriloquy below the level of the seventh cervical vertebra; lloch- singcr's sign of glandular enlargement in the fourth and fifth intercostal spaces in the median axillary line. This condition of enlargement of the bronchial glands is much more com- mon in children than in adults, and it predisposes to the invasion of the tubercle bacillus although the pri- mary infection maj^ be due to grippe, whooping cough, measles, or sj'philis. A radiograph will either prove or dis- prove its existence. Trivino (La Medicina Ibera, Mar. 20, 1920). DIAGNOSIS.— Chronic adenitis is generally limited to one or two irlands ; when the glands are tuber- culous, chronic adenitis is apt to affect an entire mass. The former is often associated with an external simple lesion ; the tuberculous form is apt to be more frequent in children, young- soldiers, and negroes. A fragment of the suspected tissue may be implanted into the subcu- taneous connective tissue of the groin of a guinea-pig, and if the specimen is tuberculous a miliary tuberculosis will develop in from live to six weeks. The use of the tuberculin test in the diagnosis of tuberculous adenitis is reliable and harmless. The tuber- culin used is a 1 per cent, solution of Koch's original product, from 1 to 5 mg. constituting a usual dose. If in from six to twenty-four hours after the injection of tuberculin solu- tion there occur weakness, sensations of heat and cold, general malaise, nausea, anorexia, severe headache, pain in the back and limbs, and if these symptoms are sharply defined in both their beg^inning and ending, reaction is considered to have oc- curred. Supraclavicular adenitis, while fre- quent in phthisis, is not present in every case. It is. however, of great diagnostic ADENITIS (WITHERSTINE). 359 value when present. There may be few or many slightly enlarged glands, and they are frequently bilateral. The writer examined over 300 chil- dren from infancy to 13 years of age from the Infants' Hospital, from a large school and from private prac- tice, X-ray being employed to con- firm d'Espine's sign. While the point on the vertebral column at which whispered voice changes from a vesicular to a bronchial character was given by d'Espine as taking place at the 7th cervical in a few cases, the writer found the change as high as the 7th cervical, but commonly at the 1st and 2d dorsal, and frequently as low as the 3d without cause. The average height was found to increase with age. [D'Espine's sign is described on page 352]. The writer, therefore, regards as a positive d'Espine a change in char- acter of whispered voice or expiration at or below the 3d dorsal. He thinks it advisable to think of these glands as of those up and down the trachea, and of those at the root of the lungs. Inflammation of both of the sets will give positive d'Espine, dullness ac- companj-ing those at the root of the lungs, and not with glands down the trachea unless there is also consolida- tion at the apex of the lungs. W. W. Howell ( Amer. Jour. Dis. of Children, Aug., 1915). Lymphadenoma. — This variety of tumor is usually more voluminous and is not suppurative. The diagnosis, how- ever, is exceedingly difficult. Simple Adenitis. — This is an acute affection usually ending in a few days in suppuration. Syphilitic Adenitis. — When a pri- mary sore is present, numerous, small, hard, indolent glands can be felt if the region is supplied with a chain of lym- phatics. When in secondary syphilis there is glandular enlargement, a large nuinber of external lymphatics take part in the process. Carcinoma. — The enlarged glands are small and hard, and can generally be distinctly traced to the growth. Lymphosarcoma. — This persists longer and is much larger before de- generation occurs. Chronic adenitis is frequently a com- plication of malignant tumors. Supra- clavicular adenitis appearing during the course of visceral cancer is usually situ- ated on the left side (found 27 times on that side by one author). It may be solitary or accompanied by adenitis in other regions ; it usually appears late and develops rather rapidly. When occurring early it may be very useful for diagnostic purposes. From a clinical point of view this adenitis may be known by its ligneous hardness, its painlessness, its freedom from adhesions, and by the union into one solid mass of all the glands forming it. ETIOLOGY.— This form of adeni- tis frequently follows some neighboring superficial lesion, such as eczema, impetigo, conjunctivitis, or the exan- themata. Catarrhal inflammation of the mucous membranes predisposes to tuberculosis of the glands. The resist- ance of the lymph-tissue is weakened. This explains the frequent development of tuberculous bronchial adenitis after whooping-cough and measles, and of mesenteric adenitis in children with intestinal disturbances. Cervical adenitis is not a manifesta- tion of an already generalized tuber- culosis ; the bacillus penetrates, by solu- tion of continuity of the mucous mem- branes or the skin, to the ganglion, which becomes a seat of infection (Duhamel). Enlarged glands of the neck are not, primarily, tubercular, and bear the slightest relation, if any, to general or 360 ADENITIS (WITHERSTINE). pulmonary tuberculosis. They are due to a mixed infection of pus-producing bacilli, and will quickly resolve if the source of the infection is removed before the glandular tissue becomes disorganized. A distinction should be made between hereditary (congenital) and acquired tuberculosis. In the latter case the author's views seem rational and cor- rect, being comparable with and analo- gous to the phenomena observed in carcinoma and syphilis. When the in- fection is acquired there is, at first, a local seat, or focus, of infection in which the disease germs develop and from which, after proliferation, they spread until the disease becomes more or less generalized, — the germs being transmitted through the lymphatic sys- tem to the lungs and thence in the blood-stream to the various organs of the body; the various glands along the course or path of transmission become affected and in turn become additional possible foci of infection. On the other hand, when the trouble is hereditary the glandular manifestation is an indi- cation of an already generalized tuber- culosis. Youth predisposes to caseous adenitis on account of the predominance at that period of the lymphatic system. Crowding, humidity, and bad or insuffi- cient food are also predisposing factors. Tuberculous adenitis is frequently ob- served in temperate regions. Negroes brought to such climates are especially prone to become sufferers. The absorbent power of the lym- phatic system is so great that the mor- bific principle of tuberculosis may be transported to the glands without visible external lesion of the skin or mucous membrane. Axillary adenitis is frequently sec- ondary to chronic tubercular lesions of the lungs (Lepine). The cervical glands are occasionally found affected in phthisical patients. Observations by Mitchell, of Johns Hopkins Hospital, upon 170 cases of tuberculous cervical adenitis show the disease to be more prevalent among negroes than among whites, males pre- ponderating over females in the pro- portion of 3 to 2, the majority being between 10 and 30 years of age. A family history of tuberculosis was pres- ent in about half the cases, though only 4 per cent, showed positive evidence of the disease in the lungs. The condition is regarded as a local manifestation of infection through the tonsils, adenoids, or carious teeth. PATHOLOGY.— Usually an entire group of glands is affected. The glands are isolated when the irritation and rapidity of growth are not great ; this usually occurs in secondary visceral adenitis. In other cases — especially when the glands are superficial, where the adenitis is primary — the glands are united into a large lobulated and irregu- lar mass, the size of which may vary from that of a small nut to that of an orange. If the adenitis follows a visceral tuberculosis the afferent lymphatics show, in some cases, signs of tubercu- losis, as is the case in pulmonary and mesenteric tuberculous meningitis. Two varieties of lesions are to be noted: 1. Lesions of chronic adenitis affecting the stroma and the elements of the gland, which becomes hyper- trophied. 2. Specific lesions of tuber- culosis, consisting in miliary granula- tion at first, ending in caseation. As one or the other of these two processes is the more prominent, so will the lesion vary in appearance. Deep adenitis is ADENITIS (WITHERSTINE). 361 never so sclerous as the superficial appeared, but the spores remain, and variety, the latter being characterized are capable of reproducing the disease, by a more vigorous reaction. Suppuration is due to a secondary in- On section of a gland in the early fection by pyogenic micro-organisms, stage of tuberculous infection we find The virus of tubercular adenitis is it redder than usual, though at times less potent, for the caseous material of gray and somewhat translucent. The a lymph-gland kills guinea-pigs, while tuberculous granules may be perceived rabbits escape, the latter being less sus- by a glass. They are formed from the ceptible to tuberculous infection, vascular and lymphatic vessels found Taken as a whole, tuberculous adeni- in the cortical and medullary portions, tis (a) is a local disease which may fre- and resemble ordinary follicles, but quently undergo (b) spontaneous reso- contain many small cells. Caseation lution, but which (r) frequently tends rapidly occurs in them, beginning at the to suppuration, the pus being nearly center of the cells, where giant-cells are always sterile. It is, however, a con- first formed, proceeding to coagulation stant danger to the system. necrosis and caseation. A number of Chronic adenitis may, in some cases, these granulations united form the be due to continued irritation; ulcers; small, yellowish masses, which may be chronic lesions of the skin or mucous seen by the unaided eye. Caseation is membrane of the bones; periosteum; due to vascular obliteration. articulations; chronic inflammation of The small, yellowish masses, softened the viscera, and certain new growths at their centers, are surrounded by where the adenitis is purely irritative fibrous tissue due to sclerosis of the and not yet specific, stroma of the gland. When this tissue PROGNOSIS. — A chronic adenitis gives way, several masses form a large may end in resolution, suppuration — collection of yellowish, softened mate- caseation (see Pathology), cretaceous rial resembling putty. Calcification may formation, or cyst formation. If all occur when the process is very slow. the tuberculous matter can be elimi- The specific lymphadenitis blocks the nated, either by nature or art, a re- lymph-spaces and thus, for a time at covery may be obtained. The deeper least, mechanically prevents the bacilli glands are more dangerows than the from penetrating into the general circu- superficial, as they are extirpated with lation. Glands not in the stream become more difficulty. The great danger of infected, this probably being due to the local tuberculous adenitis is that it may transportation by migrating cells of the give rise to other tuberculous lesions, motionless bacillus. However, infec- either local (pulmonary phthisis, tuber- tion usually takes place in the direction culous osteitis, white swellings, or ab- of the lymph-current. As the lymph- scesses) or general (generalized tuber- spaces are obstructed by inflammation culosis, with rapid death), products, and entrance of fresh bacilli Acute miliary tuberculosis may be into the gland is thus prevented, it is caused in two ways : either by convey- the multiplication of those already ance through the lymphatic system entered into the gland which gives rise until the venous system is reached or to the tuberculosis. When caseation by the perforation of a vein and occurs, nearly all the bacilli have dis- the entrance of tuberculous material. 362 ADENITIS (WITHERSTINE). TREATMENT.— The general treat- ment should, in all cases of adenitis, receive considerable attention. Good food, country air, and sea bathing are of the greatest value. In peribronchial adenitis the same general methods are to be resorted to. When due to tuberculosis and kindred diatheses and uncomplicated by fever or involvement of lung-tissue, the sea- shore or the country is indicated. At the seaside children should not bathe in the sea, and should be as quiet as is consistent with life in the open air. Brisk frictions, milk, a nutritious diet, and iodotannic syrup (2 to 4 teaspoon- fuls per day) are efifectual measures. After three to four weeks, emulsion of calcium lactophosphate and codliver oil should be given. Counterirritation between the shoulder-blades favors the curative action of the other remedies (Marfan). Applications of tincture of iodine between tlie shoulders, or in some cases blisters or, even better, ignipuncture, will fulfill the latter indi- cations. The syrup of the iodide of iron, tincture of iodine, potassium io- dide, or large doses of codliver oil, already mentioned, either alone or with cinchona wine, arsenic, or ar- seniate of sodium, are the standard remedies usually recommended in these conditions. Not much is to be expected from them, however, unless outdoor life is insisted upon. Extirpation is indicated when internal remedies and X-rays have failed ; when glands involve the face and produce de- formity; when they are isolated and few in numbers; when they have un- dergone fibrous degeneration ; when tlicy are not freely suppurating. It is contraindicated when there is impaired general health and tubercular deposits in the lungs and joints; when ramifica- tions of the chain of glands are very extensive. The writer treated 30 cases of tuberculous adenitis with X-rays, and obtained prompt recovery. It proved so effectual that it can be relied on to differentiate ordinary tuberculous glands from Hodgkin's disease, as in his 5 cases of the latter disease not the slightest benefit was apparent. It even seemed, in fact, as if some of the cases had been aggravated. J. and S. Ratera (Siglo Medico, July 21, 1917). In a group of 48 cases of tuber- culous glands, complete . cure was realized in 35. Only 2 others failed to show marked benefit, though im- proved. A great advantage of the treatment is that the healing pro- ceeds without leaving disfiguring traces. From 8 to 10 exposures were the average course, some cases need- ing very few and others requiring a whole year. The exposures were about 4 H. units and the intervals about 3 weeks. Van Ree (Xederl. Tijdsch. V. Geneesk., Sept. 1, 1917). Cervical adenitis is a frequent dis- ease and deserves more serious con- sideration. Each case should be studied as an individual, and every means employed that will produce beneficial results. Rontgen rays can be expected to relieve completely the early cases. Softened glands should be opened and drained as abscesses. Patients who have been operated upon should receive postoperative treatment to prevent recurrences. G. E. Pfahler (N. Y. State Jour. Med., xviii, 99, 1918). The end-results in the treatment of tuberculous adenitis by X-rays are superior to those produced by anj' other method, because radiation is a local as well as a constitutional treat- ment, ^lore cases are permanently cured by this method than by sur- gery alone. Rontgenotherapy never spreads the tuberculous process, leaves no deformit3\ and the patient always gains in weight and general health during treatment. R. H. ADENITIS (WITHERSTINE). 363 Boggs (Amer. Jour. Roentgenol., v. 425, 1918). Brilliant results reported from radiotherapy of tuberculous glands. Improvement obtained in all of 470 cases and a clinical cure in 85 per cent, within a few months. The more malignant processes usually require preliminary surgical measures. The benign type may be larger, but they retrogress under a few exposures. A cheesy agglomeration of lymphomas may require 6 or 8 exposures at 3- week intervals, and after this a few treatments at 3-month intervals. The cheesy matter can be aspirated through a large needle, and any par- ticularly favorably located single gland can be excised. Painful glandu- lar processes, if solitary, had better be excised, followed by 6 exposures. If inoperable, the exposures alone must be the reliance. When com- bined with an abscess, the writer ad- vises incision with 1 exposure a week, never exposing red skin; otherwise scarring results. Van Ree (Nederl. Tijdsch. V. Geneesk., Nov. 13, 1920). The possibility of giving rise to a tuberculous process elsewhere by facilitating absorption through ex- posed tissues should be borne in mind. In all cases of cervical adenitis the tonsils should be removed as the first procedure. If the glands are not broken down, and an operation on them has to be performed, then the tonsil should be removed at the same time. Removal seems to be followed by no deleterious effects, while the tonsil may afford entrance for rheu- matic infection. Richards (Boston Med. and Surg. Jour., Jan. 7, 1915). As shown below prudence is necessary in the removal of diseased tonsils, lest general infection result if tubercle bacilli are present. Pottenger deems it necessary to emphasize the importance of prudence in this connection. Our own practice is to give the iodides internally and to treat the tonsils by means of the curette, the phenol- ated iodo-tannin glycerite (see vol. vii, page 73) and galvano-cautery if necessary to close the crypts, removing the tonsils only if necessary after these procedures have greatly reduced or eliminated the danger of systemic infection. Editors. Senn held that early operative in- terference is as necessary in the treat- ment of tubercular adenitis as in the treatment of malignant tumors, and holds out more encouragement, so far as a permanent cure is concerned. Tillmann argues that glandular tuber- ctilosis should be operated as soon as possible, in order to prevent general miliary tuberculosis by the passage of the bacilli into the system. The treatment by filiform drainage is simple and easily carried out under local or no anesthesia, and results in a cure, without any noticeable scar- ring, in about 2 weeks. In small, ■ superficial, dosed, cold abscesses in which the overlying skin is not in- flamed, he passes a large needle com- pletely through the lesion, carries 2 strands of horsehair through it, knots them to form a loop, passes through 2 more strands perpendicular to the first 2 (crucial drainage), and applies a drj' zinc peroxide dressing. In large, deep abscesses of the same kind he makes a narrow, stab in- cision, explores the abscess cavity and its pockets, with a probe or fine grooved director, and passes horse- hair from the central incision through the two poles and the various pock- ets of the abscess (radial drainage). Where' the skin is inflamed it can be kept from ulcerating by inserting crucial horsehair strands through the abscess from the sound skin; if per- foration of the skin does take place it soon closes under a dry zinc per- oxide dressing. Chaput (Paris med., Apr. 22, 1916). Rapid and complete healing is al- ways realized in the writer's cases after excision of tuberculous glands in the neck, owing to his routine pro- cedure of suturing immediately with- out draining. In more than half of his 63 cases the gland burst and pus inundated the field, but his assump- tion that the pus in such cases is 364 ADENITIS (WITHERSTINE). sterile was always coiilirnied t))- the healing by primary intention. Du- fournientel (Presse med.. Dec. 5, 1918). After incision, closure should be performed. The wound should be drained. The operator should not only feel, but see, every gland he removes. In cervical adenitis an S-shaped in- cision gives more room and a better cicatrix. In other regions the incision should be made so as to bring its axis parallel J^P Sigmoid incision for tlie removal of cervical glands. (Senn.) with the cutaneous folds. Local recur- rence should be treated in the same way. Three or four operations in as many years have been performed by Senn on the same patient, -with final successful result. Mitchell, of Johns Hopkins Hospital, uses a T-shaped incision when making a radical operation for removing all the glands and surrounding fat. The long arm of this incision is made to curve forward over the sternomastoid muscle and starting from the mastoid process joins the short arm along the cla\''icle, the dissection being carried from below- upward and outward from the mesial line, the external jugular vein being tied with two ligatures and divided be- tween them. The omohyoid muscle is then divided, and by using it as a retractor the internal jugular vein is exposed and the sternomastoid muscles pulled aside. In dissecting out the mass of glands the greatest difficulty is experienced with the chain connecting the anterior and posterior triangles behind the sternomastoid muscle, as the spinal accessory nerve passes through the mass and is generally very adherent. It is only when there is very extensive mischief that it becomes necessary to divide the sternomastoid muscle or spinal accessory nerve, or even to tie and divide the internal jugular vein, and these steps should only be resorted to when the advantages of free ex- posure outweigh other considerations. The wound is closed with a subcu- taneous silver suture and drained at its most dependent part. The resulting scar is usually slight. When many glands are involved and suppuration has occurred, or when peri- adenitis is present, excision is not to be recommended, as extensive connective- tissue infiltration renders it impossible to remove all the infected tissue. Subcutaneous extirpation ma}' be resorted to, but the method allows of but imperfect evacuation of the glan- dular contents and is unsatisfactory. Drainage of the abscess is a measure which may be recommended for many reasons. A small incision is sufficient for all purposes, and there is practically no scar left. Mesenteric tuberculovis glands should be removed if possible. They are usu- ally discernible as persistent movable tumors beneath the abdominal wall, with anorexia, loss of weight and strength, occasional fever, colicky pains, and possibly nmcous in the stools with a tendency to diarrhea. ADENITIS (WITHERSTIXE). 365 Less radical measures sometimes bring about a cure. A transformation of the tuberculous tissues into a scle- rotic mass may be obtained. A solution of chloride of zinc injected about the tuberculous foci excites a growth of new fibrous tissue, which encapsulates the diseased portion. Solutions of iodoform and ether (iodofonn, 1 part; ether, 5 parts; dis- tilled water, 5 parts. Injection not to be repeated while iodofonn is being excreted in the urine), after Verneuil, in cases where operative procedures are indicated, give a lasting cure, without a cicatrix. These injections seem to exert a beneficial action not only on the tuberculous glands treated, but also on those at a distance from the seat of the injection. Robin uses an injection, iodoform, 1 part ; ether, 10 parts ; oil of sweet almonds, 100 parts ; creosote, 2 parts. Camphor-naphthol has proved valu- able in some cases. It is prepared as follows : — B Betanaphthol, Camphor aa 10 parts. Alcohol (60 per cent.) 40 parts. A few drops are to be injected, with antiseptic precautions, here and there throughout the mass of indurated glands, as suggested by Courtin, of Bordeaux. It is claimed in favor of camphor- naphthol that there is no danger of intoxication and that the treatment is almost painless. Menard and Calot, however, have reported cases of intoxi- cation following injection of camphor- naphthol into abscess cavities. The patient sullfered from frequent, rapid pulse, loss of consciousness, and epilep- tiform attacks. The quantity of the drug injected was about 6 drams. This patient recovered. In another ca?e, 8 years of age, 1^ ounces of the solution were injected. In the third case, aged 12, 5 drams. In the last 2 cases life was saved by freely opening the cavity and washing it out on the first appear- ance of toxic symptoms. Interstitial injections, of iodine, fre- quently recommended, usually fail or cause suppuration, owing to the fact that the tincture of iodine is employed. Metallic iodine, however, gives good results ; the abscess is filled with the crystalline iodine, 8 or 10 applications usually insuring a cure. Exposure to sunlight constitutes the most eligible conservative treat- ment, being preferable because it acts upon the entire body while taking the patient away from his ordinary mode of life. Iselin (Correspondenzbl. f. schweizer Aerzte; Wiener klin. Woch., Xu. 45, 1912). Barjou, of Lyons, commends the use of the X-ray in the treatment of tuber- cular adenitis. The principal effect of this treatment is upon the general in- filtration which so often accompanies scrofula, uniting the lymph-glands in a solid mass. The glands become sep- arated soon after beginning the appli- cations, and later disappear. If there is any tendency to softening, the rays hasten this, so that the abscess may be opened earlier. The rays continue to have a good effect upon the suppurat- ing tissues. Untoward effects or tend- ency to cause metastasis are rarely noted. The late C. L. Leonard deemed it the most effective method for the treatment of tuberculous adenitis in all its varieties. It affords also the best cosmetic, as well as permanent, results. ]\Iuch evidence to this effect was ad- duced in the foregoing pages. Cases of tuberculous adenitis were formerh' given X-ray treatment to avoid unsightly scars, but to-day it is 366 ADENOID VEGETATIONS (KNIGHT AND CARISS). used l)ccause operation is followed by frequent recurrence. The X-ray treat- ment is preferable when the glands are scattered or broken down. Boggs (N. Y. Med. Jour., May 21, 1916). Twenty cases of tuberculous adeni- tis treated successfully with radium. The nodes at all stages disappeared, leaving no scar unless a sinus had been present at the beginning of the treatment. Ulceration did not occur in any case. Fifteen milligrams of radium bromide spread over an ap- plicator V/i inches in diameter, screened by 1 millimeter of silver, was strapped over the area to be treated for 10 hours. Two applica- tions a week were usually employed. After a week or 10 days the swelling began to grow smaller and at the end of a few weeks nothing but fibrous nodules were left. El. S. Molyneux Brit. Med. Jour., Nov. 29, 1919). Koch's tuberculin and the simul- taneous use of the Bier method have been used with success in tuberculous adenitis. At the Westfield State Sanatorium, Mass., patients having no more than 1 degree of temperature, and having no other signs of active pulmonary disease, are given tuberculin treat- ment, the bacillin-emulsion being used. The initial dose is one-mil- lionth of a milligram and the course of treatment extends over a period of about 6 months until the maxi- mum of 10 milligrams is reached. The glands decrease perceptibly in size and the area of dullness over the hilus becomes less pronounced. Sur- gical interference is necessary to re- move only such glands as have be- come caseous or fibroid. H. D. Chad- wick (Boston Med. and Surg. Jour., Jan. 7, 1915). Of 40 cases of surgical tuberculosis treated by the writer with tuberculin, 19 had glandular disease of the cer- vical group, 1 case showing also in- volvement of the axillary group. Of the joint cases, the hip was involved in 6. In 4 cases the vertebra were affected. Of the 19 cases, 12 were discharged as well, 6 improved, and 1 unimproved when last seen. Sieber (Amer. Jour. Med. Sci., Sept., 1917). C. Sumner Witherstine, Philadelphia. ADENOID VEGETATIONS.— DEFINITION.— A definition of ade- noid vegetations, or adenoids, must be somewhat elastic. The name tonsil is often applied, and we hear pharv'ns^eal tonsil, third tonsil, Luschka's tonsil, or bursa, used indiscriminately. It would be well to restrict the term tonsil to the lymphoid aggregation between the pillars of the fauces, where it was first employed. The word adenoid seems to have been pro- posed nearly two thousand years ago (Wright, "The Nose and Throat in the History of Medicine"), is there- fore sanctified by time and usage, and will doubtless be permanently re- tained. Lymphoid tissue is a normal con- stituent of mucous membranes, but the question : When does it become patho- logical ? is not easy to answer. On the one hand we are told that it is abnormal "when visible to the naked eye," and on the other "when it causes subjective symptoms." Many insignificant hyper- plasi?e cause a good deal of disturb- ance, and on the contrary in a stolid, phlegmatic child or in a phar\mx of large dimensions very considerable hypertrophies often seeiu to interfere but little with comfort or health. An accurate definition is desirable, but in view of the fact that lymphoid tissue is a recognized avenue for invasion of the system by pathogenic germs it is inost iiuportant to determine in what condition of this tissue, healthy or diseased, the process of invasion is favored. Clinically it is clear that, when diseased, it is no longer capable ADENOID VEGETATIONS (KNIGHT AND CARISS). 367 of performing its physiological function and is a detriment to health quite apart from effects due merely to mechanical obstruction. The general symptoms present can hardly be explained on the latter ground alone. A species of toxemia must be also concerned. Dis- tended crypts provide an excellent bed for the cultivation of germs, which find ready access to the circulation in the absence of effective resistance. Lym- phoid tissue may be a portal of entry without itself showing marked patho- logical change, while it is probable that a dense fibrous adenoid, as met with in older subjects, may offer a firm barrier to bacterial assaults. In keeping with Harris and others, the writer looks upon adenoids as de- fensive structures in prolonged ex- posure to pathogenic agents. S. G. Vicente (Rev. de Med. y. Cir. Pract., July 14, 1915). The writer lays stress on the close relationship between the nasopharyn- geal glandular structures (adenoids, etc.) and the pituitary body. Not only are the functions of the latter morbidly influenced, but the results of adenotomy or other local treat- ment of these pharyngeal tissues — rapid growth and improved nutrition, relief of aprosexia and morbid som- nolence, etc. — indicate to what ex- tent the pharyngeal tonsil and the pituitary s}-stem are related. The cases of retarded growth relieved by adenotomj' suggest, moreover, that adenoids inhibit the nutritional or developmental function of the pituit- ary system which we have come to understand as necessary for normal development. In a former article the author pointed out that the "ade- noid" region was the part of the nasophar^'nx most assailable by in- fection, and that the angle of this . region was the most vulnerable spot in the whole body. W. Sohier Bryant (Amer. Jour. IVIed. Sci., July, 1914; Med. Rec, Sept. 9. 1916). In certain adenoid subjects a psy- chic syndrome may be observed, especially in adolescence, which con- sists in a marked deficiency in mem- ory, somnolence or insomnia, lack of power to fix the attention, and in in- tellectual weakness. This syndrome inay even be observed in various dis- eased conditions of the nasopharynx and sphenoid regions, especially tumors. It is probably of hypophy- seal origin. The writers report the details of 3 cases observed in sol- dier , having a history of adenoids which had not been treated and rem- nants of which still persisted. The syndrome was marked in all 3, along with very manifest feminism. CitelH and Caliceti (Policlinico, xxv, sez. prat., 245. 1918\ SYMPTOMS AND DIAGNOSIS. — It is not safe to rely upon the so- called "adenoid facies" as a diagnostic sign. A very similar appearance is sometimes seen in a subject of intra- nasal obstmction, while the postnasal space is quite free. A typical case of adenoid hypertrophy in the vault of the pharynx usually wears a dull, listless expression. The nostrils are narrow and pinched ; tlie bridge of the nose by contrast seems widened. The upper lip is retracted, exposing the teeth of the upper jaw, which project and overlap those of the lower. The upper jaw is compressed laterally, so that the roof of the mouth is converted into a Gothic or \'-shaped arch. Deflection of the nasal septum may be a result. The nasolabial folds are effaced, and the transverse vein at the root of the nose is unusually conspicuous (Scanes Spicer). The child has a pasty, sallow complexion, and the cervical glands are prominent. The nutrition of a nursing infant suffers in consequence of fre- quent interruptions due to need of get- ting air through the mouth. For a similar reason older children "bolt" 368 ADENOID VEGETATIONS (KNIGHT AND CARISS). their food, which being defectively in- salivated causes gastric derangement. The latter is further aggravated by catarrhal secretion, always in excess in these cases, finding its way into the stomach. Loss of appetite and malassimilation are natural sequels. In severe cases deformity of the chest, pigeon-breast (Dupuytren), re- sults from the bad constitutional state, the labored breathing, or from both combined. The mental dullness shown by these children is referred to inter- ference with the lymphatic drainage of the brain and to impaired hearing. An investicration of the occurrence of adenoids in three London elenien- tarj' schools, with an attendance of 2315, showed that, on the average, about 37 per cent, of the children in elementarj- schools have adenoids, and that between 72 and 76 per cent, of these have enlarged tonsils as well. On the average, 31.2 per cent, of ade- noid cases are mouth-I)reathers, com- plete or partial, and hypertrophy of the faucial tonsils may give rise to mouth-breathing in the absence of adenoids. Sex appears to have no in- fluence upon the incidence of ade- noids. Adenoids are more common about the age of 8 years, and are next most frequent at about 12 years. True aprosexia is often confused with ap- parent dullness, due to defective hear- ing, and it occurs in only about 4.7 per cent, of adenoid cases, is more fre- quent in girls, and, when present, is associated with a marked degree of adenoids. Macleod Yearsley (Brit. Jour. Child. Dis., Feb., Mar., 1910^. Gritting of the teeth at night was noted in 34.4 per cent, of a series of 500 cases of adenoids by the writer, and is believed by him of diagnostic value. Benjamins (Nederlandsch. Tijdschr. v. Geneesk, July 17, 1915). "Growing pains" are due to ade- noids in fidgety children with con- stant slight fever, slight cervical glandular enlargements, and a muf- fled first heart sound; great improve- ment follows adenoidectomy in these cases. H. O. Butler (Lancet, June 26, 1915J. The term aprosexia has been given to lack of ability to concentrate (Guyej. Mouth-breathing is a source of much discomfort and even danger. The membranes of the whole respiratory tract suffer from inhalation of improp- erly prepared air. Snufifling and noisy breathing by day and snoring at night are often distress- ing. Sleep is much disturbed thereby as well as by bad dreams, "night ter- rors" {pavor nocturnus) resulting from deranged cerebral circulation. The ef- fect upon the voice is characteristic. Its non-resonant, "dead" quality always suggests adenoids, at least in young sub- jects. The ability to precisely locate an obstruction from the sound of the voice, claimed by some, seems to be hardly warranted. In addition to special difficulty with the nasal con- sonants speech in general is thick and unpleasing. Actual stammering and stuttering have been ascribed to ade- noids, and a long list of reflex neuroses aft'ecting the eyes, the ears, and more remote organs has been compiled. /Vmong them may be mentioned laryn- geal spasm, hiccough, asthma, hernia, prolapse of the rectum, nocturnal enuresis, chorea, and epilepsy, some of which no doubt have their origin in the imagination of the observer. The rela- tion of laryngeal neoplasms to adenoids is a question of much interest. Even if we decline to accept a theory of "ver- rucous diathesis," or special predisposi- tion to neoplastic development, it is reasonable to assume that habitual mouth-breathing nuist irritate the laryn- geal mucosa. It has also been sug- gested that secretions find their way from above into the vestibule of the ADENOID VEGETATIONS (KNIGHT AND CARISS). 369 larynx, and, again, that the extraordi- nary labor imposed upon the larynx during- phonation under these circum- stances favors the formation of new- growths. Many excellent observers maintain, however, that neoplasms of the larynx are not especially common in adenoid cases. Frequent attacks of earache, In a large number of school chil- dren who sufifered with blurring vis- ion and fatigue on reading, the author found nasopharyngeal hypertrophy to be the real cause of the symptoms. W. M. Killen (Brit. Med. Jour., Sept. 25, 1909). The writer observed a child with mild bilateral exophthalmos, relieved by adenoidectomy. W. C. Posey (Pa. Med. Jour., July, 1912). Posterior rhinoscopic view. (After Grunwald.) of nosebleed, and a tendency to catch cold, are generally included in the list of symptoms. Headache and asthe- nopia are complained of, the senses of smell and of taste are impaired, and frequently an ichorous discharge excoriates the nostrils and upper lip. Attacks of petit mal in a child may also be due to adenoids. Impairment of hearing, chronic otorrhea, profuse nasal discharge sug- gesting sinusitis and sinusitis are fre- quently associated conditions. The picture in the rhinoscopic mirror is unmistakable. Lobulated or fissured masses of various sizes are seen hang- ing from the vault of the pharynx, obscuring the arches of the choan?e, and often filling the fossae of Rosen- miiller and covering the orifices of the Eustachian tubes. They have been likened in appearance to a "cock's comb" (Czermak, 1860). and they are spoken of by Voltolini (1865) as "stalactite-like growths," a term adopted by Morell Mackenzie. They are often 1—24 370 ADExXOID VEGETATIOXS (KXIfillT AXD CARISS). visible by anterior rhinoscopy when the intranasal structures have been shrunken by atrophy or retracted by cocaine. Sometimes tlie vegetations arc distributed down the posterior wall of the pharynx, below the plane of the velum, or they may push forward into the nasal chambers. The view may be masked by viscid or in- spissated secretion, and, being fore- shortened in the mirror, does not give an adequate idea of the volume of the growth. In some cases, generally in Adenoids seen through anterior nares. (After Griinwald.) older subjects, the mass is more uni- form and cushion-like in appearance, or is bilobed, being divided by an anteroposterior median furrow (reces- stts pharyngcus meditis), and is less vascular looking. In adults remnants of adenoids are often seen in the form of bands between the Eustachian cushion and the pharyngeal wall, which doubtless bear some relation to various subjective aural disturbances. Applications of cocaine and the use of a palate retractor are to be recom- mended only in older children and when a rhinoscopic examination is imperative. By the exercise of tact and patience it is often possible to get a view, even in a very unpromising case. In some it is out of the question and the only resource is a digital examina- tion. The process is disagreeable to the patient and dangerous for the examiner in children, unless one's finger is pro- tected in some way. A finger shield of metal or rubber may be used, or a mouth-gag may be applied. Better still, the child being firmly held by an assistant, the examiner standing on the left presses the right cheek of the patient between the separated jaws with his right middle finger while he quickly passes his left forefinger into the open mouth and up behind the velum. The mouth cannot be closed and thus the finger is safe. The anatomical landmarks to be sought are the posterior margin of the vomer in the middle line and the Eu- stachian eminences at the sides. A novice might mistake a prominent Eustachian cushion, a papillated pos- terior end of an inferior turbinate, or even the contracted velum (E. 11. Hooper) for an adenoid mass, but the last is higher in the fornix of the pharynx and more posterior and has a distinctly lobulated, elastic, and pulpy feeling, compared to that of a bunch of earthworms. On withdrawal the fin- ger is smeared with blood, which is not the case when a healthy ])harynx is ex- plored, unless excessive force has been exercised. In those who object to the finger some idea of the extent and con- sistence of a postnasal growth niay be gained by palpation with a stift' probe or the edge of a rhinoscopic mirror. In some cases a very beautiful view of the vault of the pharynx is given by the ingenious electric pharyngoscope de- vised by Hays. The end of the instru- ment having been passed into the oro- pharynx the patient is instructed to close the lips and breathe quietly ADENOID VEGETATIONS (KNIGHT AND CARISS). 371 through the nose. The palatal muscles relax and permit the light to flood the cavity of the rhinopharynx. With a little patience and care a complete picture may he obtained., even in very sensitive throats. Nasal polypi, retro- pharyngeal abscesses, syphiloma, and neoplasms, benign or malignant, may occur in this region, but usually present features or give a history which serve to distinguish them. Benign nasopharyngeal polypi, stud- ied in 22 cases. They are usually uni- lateral and solitary, and have a peculiar pear-shaped form, the broad end lying in the nasopharynx, while the stalk ex- tends into the nose. They may attain considerable size, and are subject to in- flanunatory changes which may end in partial or total gangrene. The treat- ment is very favorable, as they are easily laid hold of, and readily torn out on account of their slender stalk. In the majority of cases the polypi do not recur. There is usually a profuse dis- charge of serous fluid after the extrac- tion, and examination of the antrum shows a slight chronic inflammation. Choanal polypi originate within the antrum of Highmore, and are due to inflammation of the antral mucous membrane. Killian (Lancet, July 14, p. 81, 1906). It is hard to believe that a simple pendulous polypus of the nasopharynx could be mistaken for a bunch of ade- noids. Yet the risk is evidently present in the minds of some observers. In a paper by W. A. Wells (Laryngo- scope, July, 1911) the fact is noted that it is usually taken for granted that postnasal obstruction in a child under 15 years is due to adenoids. He describes 3 cases of fibrous polypus, which he makes the basis of a plea for intranasal removal with the cold-wire snare rather than, by a "mutilating" external operation generally employed in growths of this kind. He enumer- ates three theories of etiolog}' : (1) cranial, propounded by Nelaton; (2) choanal, that is, springing from the ethmoid, sphenoid, or vomeral region, and (3) sinusal, as adopted by Killian in the paper above quoted. While it is well to bear them in mind, fibrous polypi of the pharynx are so rare and their symptoms are so different from those of adenoids, except in the single feature of obstruction, that the chance of confusion is rather remote. Rugse or folds of thickened mucous membrane in the floor of the nose, and the so-called "lateral bands" of red and thickened membrane on the walls of the phar}-nx behind the posterior pillars {pharyngitis lateralis Jiypcrtropica) are regarded by some as pathogno- monic, but each is often found without adenoids. Fluid injected into one nos- tril is expected to escape by the other if the nasopharynx is free; by the mouth if adenoids are present (Semon, quoted by Schech). A similar test with oil spray is regarded as "almost abso- lutely diagnostic'' (Bosworth). Each of these experiments must be invali- dated by a unilateral nasal stenosis and shovtld not be relied upon. Adenoids may exist without enlarged laucial tonsils: the reverse is seldom true. Hence it is important to examine the pharyngeal yault in all who mani- fest the latter condition. The occur- rence of adenoids, as well as of tur- binate hypertrophy, in victims of cleft palate has often been remarked, whether as an effort of nature to stop the gap or as a consequence of the same diathesis that caused the palatal deformity is hard to decide. Such cases afford unusual opportunity for study of these anomalies. ETIOLOGY.— A constitutional state allied to struma, termed lymphatism Z72 ADENOID VEGETATIONS (KNIGHT AND CARISS). (Potain), predisposes to lymphoid hy- perplasia. From observation of 1995 cases Sendziak concludes that "scrof- ula" plays an important part in etiology, a view shared by Lennox Browne. The exanthemata, syphilis, tuberculosis, are similarly accused. Poor sanitation, bad hygiene, and im- proper diet are undoubted factors, yet not infrequently cases occur in which none of the foregoing elements is concerned and we are at a loss to dis- cover the cause of the condition. The importance of nasal stenosis, resulting perhaps from some injury in early life, is generally admitted. Be- hind an obstruction the air is so rare- tied on inspiration that congestion of the mucous membrane results with consequent tendency to hyperplasia. The bearing of this fact with refer- ence to treatment should be appreci- ated. The habitual breathing of im- pure air, or of air too hot or dry, often prevailing in our homes and sleeping rooms, no doubt has a bad effect on the mucous membranes. The same is true of certain occupations that in- volve the inhalation of irritating va- pors or floating matter in the air. The condition occurs with equal fre- quency in the two se.xes. It seems reasonable to admit an inherited pro- clivity. Those who deny the exist- ence of heredity find it difficult to ex- plain the exhibition of almost identical local conditions in several successive generations. The effect of a rigorous climate is not necessarily bad. but ex- tremes and sudden changes of temper- ature and humidity are no doubt harmful. Adenoid growths are essentially a disease of early life, of the formative period, when the lymphoid tissues are especially active. A few congenital cases are on record. Among 437 chil- dren in the first three years of life examined by W. F. Chappell not a single example of lymphoid hyper- trophy under the age of three months was found. R. G. Freeman has rightly criticized the neglect of adenoids in early infancy, as they interfere with the proper develop- ment of the child by reflex action, by the irritation they produce and the obstruc- tion they cause. The postnasal pharynx at birth is a space only one-quarter inch high by one-third inch wide, so that a very slight adenoid hypcrtrophj' at this period will cause obstruction. At the end of the first year it is nearly doubled in size. It often produces symptoms in the first days of life, and the mistake is sometimes made of diagnosing specific disease. The snuf- fles are specially marked while the child is nursing and result from an adenoid which produces irritation, and, if large enough to obstruct the pharynx, there is mouth-breathing. A survey of 1064 operations for the complete removal of tonsils and aden- oids caused the writer to wonder whether all these operations are really necessary. The removal of adenoids in the so-called idiopathic asthma of the nervous, wheezy child has no beneficial effect, and most of these children have no adenoid growth. Idiopathic asthma must not be confused with the intermittent suffocative attacks during sleep, which are due to adenoids, and are cured by the removal of the growth. A large nimiber of children have attacks of earache and deafness during colds, with retraction of the drums, which frequently suppurate; and if such a case is allowed to continue without operation, the deafness or dullness ot hearing becomes permanent, and is beyond cure. The affection of the ears makes operation imperative. The writer has carefully examined a large number of children 6 months or more after operation, and has en- deavored to follow up cases, and has not observed any deleterious effects ADENOID VEGETATIONS (KNIGHT AND CARISS). 373 or disadvantages following removal of tonsils and adenoids. He has not obtained any evidence to indicate that the removal of the tonsils predisposes these children to diphtheria, scarlet fever, or other acute infections, but has seen several cases of unhealth}^ spongy tonsils yielding cultures of the Klebs-Loeffler bacillus weeks af- ter the quarantine period had elapsed. E. D. D. Davis (Brit. Med. Jour., Jan. 26, 1918). Numerous statistics are available showing- a preponderance of evidence that removal of diseased adenoids and tonsils decidedly lessens the sus- ceptibility to the contraction of the acute exanthematous diseases. Rare instances have been noted in the aged, but the tendency is toward atrophy after puberty. Several cases in elderly people have been observed by Bryson Delavan, who holds the belief that the condition may develop in middle life and is not necessarily a legacy from childhood. One was dis- covered by J. Solis-Cohen in a woman of 70, and a number of authentic cases after the age of 60 have been reported (P. G. Frank), but at this time of life a maligTiant element is always to be suspected. The curious observation has been made by Gelle that these structures sometimes show renewed activity at the menopause. The bacteriolog-y of adenoid tissue is very similar to that of the tonsils, among the infective organisms being staphylococci, pneumococci, strepto- cocci and at times the Klebs-Loeffler bacilli and the tubercle bacilli. A sur- prising number of cases show the streptococcus hemolyticus and strep- tococcus viridans. PATHOLOGY.— Lymphoid cells embedded in a reticulum of connective tissue containing small blood-vessels and ner\-es, the retiform adenoid tis- sue of His, and enclosed in a mucous membrane covered by columnar cilia- ted epithelium, constitute adenoid vegetations. The relative proportion of these elements varies with the age of the patient, the duration of the dis- ease, and the frequency and intensity of acute inflammatorv attacks, to which this tissue is verv liable. In young subjects cells predominate and the tissue is soft, friable, and vascular; in older ones connective tissue is in excess and the mass is more dense and hard. As a matter of clinical convenience adenoids are sometiines divided into soft and hard, which are, of course, merely grades of the same patholog- ical process. In very young children, also, a temporary intumescence takes place in consequence of gastrointesti- nal disturbance or other cause, when many of the subjective symptoms of adenoids are presented. This condi- tion, naturally, calls for different treatment than an organized hyper- plasia. Morbid changes are not con- fined to the epiphar\-nx, but involve adjacent lymphoid structures. Cystic transformation and other disorders of the phar\'ngeal bursa have been par- ticularly described by Tornwaldt. A cyst of the bursa may reach extreme dimensions and occasionallv small cysts are met with in the adenoid tissue, but the importance of these conditions has been somewhat ex- aggerated. The idea once expressed by W'oakes that adenoid vegetations are papillomatous is not sustained. PROGNOSIS.— Under present-day methods of attacking the disease the prognosis is good, both as to arrest of the morbid process and relief of asso- ciated symptoms. Only in case the con- dition has been extreme in degree or ^'4 o/- ADENOID VEGETATIONS (KNIGHT AND CARISS). duration organic changes may have been established, for example in the ears, which are irremediable. Chronic otor- rhea due to adenoids cannot be cured while the latter are allowed to persist. Likewise impaired hearing and tinnitus due to occlusion of the Eustachian tube from pressure or congestion must be reached through removal of an adenoid mass. Recurrence of adenoids may take place in certain cases of pronounced lymphatism (status lymphaticus), in which predisposing factors cannot be wholly eliminated, or when an opera- tion for removal has been done very . early in life. The suspicion remains, however, that some alleged relapses are really examples of incomplete removal. These partial operations are explained in a measure by A. A. Bliss on the ground that the lymphoid tissue pene- trates the fissures of the vomerosphe- noidal articulation {canales basis vonicri of Harrison Allen), where it is more or less inaccessible. Extreme vascularity of the region and the fact that the adenoid is often made up of separate and distinct bundles also contribute to the possibility of apj^iarcnt recurrence, which is really a growth of tissue that has evaded the knife. It is safe to say that no operation in the upper air tract confers more grati- fying and positive benefits than an adenectomy properly done. There has been much controversy as to the thor- oughness with which morbid tissue should be removed, one side advocating extirpation of every vestige and the other averring that such a course is ultraradical. When we reflect upon the wide distribution of lymphoid tissue in the so-called ring of W^aldeyer, or lymphoid triangle, the conclusion is forced upon us that absolute eradica- tion is impracticable, even if desired. What we accomplish in a given case is extraction of the most salient and dis- eased portions : the consequent im- provement in air supply and in other respects enables nature to do the rest. This statement is not to be taken as a defense of superficial operating, or as a suggestion that we may trust nature to supply defects involved in our own negligence. Postoperative shrinkage of any considerable remnants is not to be expected, these fragments showing rather some apparently compensatory hypertrophy, yet there are limits of safety beyond which we may not pass and anatomical conditions which are insuperable. Certainly erasion of the mucous membrane through its whole thickness, so as to replace glandular tissue by scar tissue, is inadvisable. Adenoid tissue is present in the vault of the pharynx in 1 out of every 4 recruits. It should be re- corded in the physical examination so that due weight may be given to it as a factor in producing defec- tive hearing when cases of this sort come up for discharge for disability or pension. AH large adenoids should be excised on entry into the service, and smaller masses if associated with pathological changes in the middle ears. Refusal to consent to opera- tion should disqualify applicants for enlistment in the artillerj- branch of the service or transfer to that branch. Every 2 out of 3 recruits who have adenoids have visible changes in the middle ears. Fifty per cent, of the cases who do not have adenoids, but who do have hypertrophied tonsils, have changes in the middle ears. Changes in the middle ears without th presence of either adenoid or tonsillar hj'pertrophy are unusual, and occur in only 1 case out of 12, and in the case in which it occurs it is usually associated with hypertro- phic rhinitis. In other words, in 11 cases out of 12 which show changes in the middle ears, adenoid or ?on- ADENOID VEGETATTOXS (KNTGHT AND CARTSS). 2,7: sillar hypertrophy will be found. One out of every 3 cases with adenoids will also have hypertrophied tonsils. Two out of every 3 cases with hyper- trophied tonsils will also have ade- noids. Recruits with marked hyper- trophy of the tonsils should have the glands excised, whether they have had repeated attacks of acute tonsillitis or not. Adenoids do not undergo spontaneous atrophy in young adults. Le Wald (Military Surgeon, May, 1910). In a small proportion of cases breath- ing by the natural channels is not at once resumed. This is due simply to the habit of mouth-breathing, or to im- perfect development of the air tract from prolonged disuse. In the former case the habit is soon corrected by some device for binding up the chin and keeping the mouth closed during sleep. In the latter the difificulty is greater and it may be a long time before the normal respiratory current is restored. These cases, fortunately rare, are most dis- appointing to operator and parents and yield, if at all, only to careful attention to hygiene and to measures tending to promote development. The co-opera- tion of the dentist is enlisted for cor- rection of the oral deformity, widening the dental arch and thus depressing the floor of the nose and increasing the diameters of the nasal passages. It is best not to delay this beyond the sixth or seventh year (E. A. Bogue), although surprising results may be achieved much later. In some cases mouth breathing de- velops without any malocclusion or nasal obstruction, the mouth simply being involuntarily relaxed. This is corrected by forced nasal breathing at night through the use of lip and chin bandages. Skilful massage of the relaxed tissues is also helpful. O. W. White (lour. Amer. Med. Assoc, Sept. 25, 19lS). Two other causes of continued diffi- culty in breathing after adenectomy have been described: one is extraor- dinary prominence of the bodies of the cervical vertebrae (J. E. Newcomb), and the other is a paresis of the sus- pensoiy apparatus of the hyoid bone and the tongue, so that, when the mus- cles are relaxed in sleep, the tongue falls back and occludes the glottis (Harrison Allen). In the experience of Payson Clark mouth-breathing persisted in Z5 out of 75 cases whose subsequent history could be learned. Over 500 others were not traced and it is fair to assume that the above percentage might be greatly reduced. Faulty habits of speech are to be re- formed by careful exercises under com- petent supervision. The palatal muscles having been long curbed in their action need to be properly educated. TREATMENT. — Until Wilhelm Meyer, in 18(^8, gave to the world the results of his careful studies, but little had been done in diagnosis or treatment of adenoids. A few scattered refer- ences are found in literature many years before his day. and the valuable researches of Luschka and others in the anatomy of this region are well known, but no serious attempts were made to remove from the postnasal region cer- tain obstructions, and their exact nature was not fully understood until Meyer began his investigations. In the hope of escaping surgery various local astringent applications and methods of treatment have been ad- vised, all of which are more or less futile, except in the vascular or "cyanotic" adenoid of some writers. In these cases instillations of adrena- lin chloride, 1 to 5000. followed bv fine sprays or vapors of mentholized albo- Z7(i ADENOID VEGETATIONS (KNIGHT AND CARISS). lene are of service. Glycerite of tan- nin and other astringents can have little or no permanent effect while the underlying cause remains. Anemia, gastrointestinal derangements, or other disorders must be corrected by proper hygiene, diet, and general medication as indicated. Internal medication offers, but little. With anemic or chlorotic children one is often inclined to temporize and tr}^ to build up the system by means of iron, and other tonics, but the speedy improvement in general condition following surgical intervention is con- clusive proof that the main cause of the constitutional depression lies in the local disorder, upon which medication alone has little or no effect. The internal and local use of iodine for its sorbefacient effect has not had success. The Bier suction hyperemia treatment, for which very temperate claims are made in hypertrophy of the faucial tonsils, does not seem to have been applied to adenoids. The tubes figured by Meyer-Schmieden for aspirating the nasal chambers and the sinuses would make Init little im- pression in the postnasal space, al- though good results in atrophy of the nasopharynx are mentioned. At one time certain "breathing ex- ercises" were loudly vaunted as a cure for adenoids. The shallow character of respiration practised by most people and the health-giving value of deep breathing are generally comprehended in these days, especially in connection with the class of cases under consider- ation. Meyer appreciated the fact that a dense hyperplasia cannot be dissi- pated by breathing exercises, or by measures tending to promote the gen- eral health, or designed to exert a con- tractile effect upon the morbid growth. His early essays at removal •were made with a small "ring knife" passed through the anterior naris and guided by a finger inserted behind the velum. It was soon found possible to operate more easily and expeditiously through the mouth, and in conse- quence today the instrument shops are flooded with forceps, guillotines, and curettes designed to facilitate this procedure. Adenoids present at birth, while never sufficiently large to endanger life, may cause obstructed nasal breathing, shown by restlessness, in- drawing of the diaphragm, and in- ability to suck. A few days after birth the infant begins to breathe with the mouth open, to snort and sniffle. Owing to the nasal obstruc- tion it swallows air while trying to suck, which makes it sick and gives it windy spasms. When removing adenoids under the age of 6 months a general anesthetic is neither required nor advisable. The infant is held in a sitting position by a nurse, a small curette is passed up behind the soft palate into the post nasal space and brought down with one sweep. It requires but a tiny pad of adenoids to cause symptoms, but in some cases one is surprised at the amount of adenoids removed. As a rule, very little bleeding takes place. The infant should be kept warm, and if there appears to be any shock, should be given a drop or 2 of brandy in a little milk. It should not be fed for 3 hours before the operation, but can be given the breast or bottle 10 minutes or so after it. Hunter Tod (Pract, Nov., 1920). In adopting a plan of operation the principles of thoroughness, gentleness, and celerity are to be observed. By the first is meant not a clean sweep of all the soft parts down to the bone, but a removal of projecting tabs that can be detected by the examining finger. The ADENOID VEGETATIONS (KNIGHT AND CARISS). 2>77 second is insured by selection of instru- ments tliat include in their bite generous segments of tissue. Thus the need of frequent reintroductions is obviated and the parts are spared unnecessary vio- lence and contusion. Finally, while undue haste is to be avoided, it is well to abbreviate as much as possible the period of narcosis. We are prone to underestimate the importance of this detail. As a matter of fact, a large proportion of accidents, both immedi- ate and secondary, can be traced to ex- cessive crowding of the anesthetic at the hands of one who is not expert in its management. Important among these is pulmonary abscess. General anesthesia should always be in charge of one trained for the duty, who knows how to get satisfactory relax- ation with a minimum of anesthetic. The fatalities in a tonsil-adenoid operation may be due to: 1. Faulty administration of the anesthetic be- cause of: (a) failure to select the appropriate anesthetic; {h) lack of knowledge, so that a deep anesthesia is mistaken for a light one; (c) fail- ure to maintain a free air passage and to watch the respiration and cir- culation; (J) failure to regulate or change the anesthetic when circum- stances alter; {e) overdosing, abso- lutely or relatively. Of these causes, (o) and (c) are more common than {c). 2. Respiratory obstruction, due to the location of the operative field just above the air passage. 3. Shock. 4. Hemorrhage. Status lymphaticus should be con- sidered as more of an idiosyncrasy; the author thinks many reported cases could have been otherwise ex- plained. As to treatment, the head should be lowered, the face sponged with cold water, the air passage cleared, either by swabbing, main- taining firm intermittent pressure on the back of the chest, by artificial respiration, or even tracheotomy. Finger pressure over the trachea and larynx through the skin is also sug- gested as a feasible means of express- ing blood clots. J. D. Mortimer (Pract., xcix, 482, 1917). Preparation of the Patient.— While adenectomy may not be properly con- sidered a major operation, yet it is by all means to be postponed in the pres- ence of any acute local disturbance, or of concurrent general disorder, or when an epidemic of any contagious disease is prevailing. The advice once given by Lennox Browne to op- erate during an attack of diphtheria, with a view of averting the necessity of a tracheotomy, is refuted by the modern mode of treatment in that disease. Locally an attempt to secure an aseptic operative field by the use of antiseptics is hopeless. The parts should be cleansed of secretion by douching with warm normal salt solu- tion, but anything beyond that is superfluous. Large faucial tonsils which interfere with manipulations should first be excised. Local application of Hess's throm- boplastin recommended as a preven- tive of post-operative hemorrhage, on the basis of 2036 adenoid and tonsil operations. J. J. Cronin (Jour. Amer. Med. Assoc, Ixvi, 557). Practically all the acute infectious diseases of childhood have followed adenectomy. The writer warns against operating in the presence of local infection or during epidemics. Much thought has been given to the reasons for unexpectedly slow and limited improvement of the patient in some instances of adenectomj^ espe- cially as regards mouth breathing. W. E. Grove (Johns Hopkins Hosp. Bull., Apr., 1913). Bleeders should be avoided, or pre- pared by a few doses of calcium chlo- ride or lactate. The strange conflict of opinion, both in the laboratory- and the clinic, as to the effect of calcium 378 ADENOID VEGETATIONS (KNIGHT AND CARISS). upon the coagulability of the blood tends to weaken confidence, but pos- sibly sliould rather teach us to use it in larger doses than has hitherto been the custom. The weight of evidence is strongly in favor of calcium lactate, some authorities asserting that the chlo- ride is practically inert (W. K. Simp- son). The former is more agreeable to take, and thus far no unpleasant con- sequences from larger doses have been experienced. Clinical experience show.s that cal- cium lactate has a controlling influ- ence in hastening the coagulation of the blood. Its efficacy is more marked in hemophilic cases where the coagulation is delayed than in cases of normal coagulation time. Before operation, especially on ton- sils and adenoids, careful inquiry should be made relative to any hemo- philic heredity or tendency. In sus- picious cases the coagulation period should be determined before opera- tion. It is questionable, if not posi- tively contraindicated, whether such operations should be undertaken in hemophilic cases other than under the most extreme urgency. In all cases of operation for the removal of ton- sils and adenoids, calcium lactate should be given for a period prior to and after the operation, both for its possible effect in diminishing the im- mediate hemorrhage and in prevent- ing secondary surface hemorrhage. Of the calcium salts, the lactate is more positive in its results, is more agreeable to administer, and is less irritating to the stomach. Simpson (Medical Record, Sept. 25, 1909). The writer submits the following hints on the tonsil-adenoid operation based on an experience of 5000 cases: 1. In middle suppuration, always ex- amine for adenoids. The same rule holds good in the familiar fleeting acute catarrhs of the middle ear. 2. In acute suppuration of the middle ear do not operate on the throat until the acute ear symptoms have sub- sided. 3. Before operating make sure that the mouth is reasonably clean. 4. Avoid passing the linger into the nasopharynx after the operation has been finished. If it is necessary, use rubber gloves. 5. Severe tonsillar hemorrhage, though often termed re- actionary or secondarj^ is seldom either. It is usually primary. 6. After all 0])erations on the nose or throat, the patient, no matter what his age, when put back to bed should not be allowed to lie on his back. He should be laid semiprone on his side with lace turned half-down, and with a basin or bowl under the mouth and nose. 7. Always visit the patient not later than three hours after the operation. 8. When about to examine the bleeding throat of a conscious patient, first of all insert a mouth- gag. 9. No case of deafness can be considered properly examined with- out the nasopharyngoscope. D. McKenzie (Pract., Aug., 1917). The bowels should be evacuated by a saline laxative and no solid food and no milk gi\'en for at least six hours beforehand. Position of the Patient. — The erect position is advocated by some, because it is that to which we are accustomed in routine work, the loss of blood is less, and debris and blood tend to escape forward rather than backward toward the glottis. Moreover it is thought that the ears are in less danger as a result of freedom from accumulations at the openings of the Eustachian tubes. The position on the side is favored by others on account of the tendency of blood and secretions to gravitate to the de- pendent side and drain ofif through the nose and mouth. After all has been said, the recumbent position seems to be the most convenient for all concerned and is free from risk, provided the anesthesia be not profound and the reflexes are preserved. In such case foreign material approaching the larynx is promptly ejected, and what ADENOID VEGETATIONS (KNIGHT AND CARISS). 379 finds its way into the stomach is thrown up before complete recovery from the anesthetic. With attention to this point, the so-called Rose's posi- tion, the head being- dependent, is not essential. When the operator selects the re- cumbent position, the body should be horizontally on the back, the head being neither flexed nor extended. With the head extended the cervical curve of the spinal column is in- creased. In this position the operator is liable to cut deeply into the struc- tures of the posterior pharyngeal wall, which will be stripped down by the curette. A lateral position favors the drainage of blood from the phar- ynx and in no way inconveniences the surgeon in removing the tonsils. For the latter purpose a small guillotine is better than a large one, and is not so liable to slip. F. C. Carle (Lancet, May 13, p. 1265, 1905). Anesthesia. — In children under one 3'ear the adenoid growth is so soft and friable that it can be readily broken down with the fingernail and no anes- thetic is necessary. An artificial nail adjusted to the fingertip (Creswell- Baber, Motais) has no advantage over a curette, and rather hampers freedom of manipulation. Local an- esthesia with novocaine, apothesine, cocaine, stovaine, or alypin is reserved for adults and for children old enough to be manageable. The writer advocates local anes- thesia, describing its advantages over general anesthesia as follows: With local anesthesia there is less danger of starting up an old tul^erculous lesion of the lungs, which occurs so frequently when general anesthesia is universally emploj'cd. General anes- thetics have been known to produce nephritis, cardiac and respiratory failure, and insufflation pneumonia. No cases of abscess of the lung liave been reported following tonsillectomy under local anesthesia. It is avail- able when general anesthesia is con- tra-indicated, as in chronic nephritis, respiratory disorders, pulmonary tu- berculosis, etc. Local anesthesia has an advantage in the rapidity with which the operation may be done without the shock which follows a general anesthetic. When the case is uncomplicated, local anesthesia is a time-saver and requires fewer assistants. Local anesthesia is contra-indicated in children under 10 years of age, in secondary operations, when there have been repeated attacks of peri- tonsillar abscess, and in highly neu- rotic adults or those with extremely sensitive throats. One-half per cent, novocame (procaine), with 1 drop of Hodo adrenalin to each dram (4 Gm.) of the anesthetic, is preferred, 1 dram of the mi.xture being injected between the capsule and muscle of each ton- sil. The same solution is used for adenoids. F. O. Lewis (Therap. Gaz., xHii, 328, 1919). The writer advocates the use of nitrous oxide anesthesia in the re- moval of tonsils and adenoids in chil- dren less than 14 years of age. In older patients cocaine and procaine are used. Yorke (Brit. Med. Jour., Aug. 28, 1920). Although certain statistics, like those given by C. A. Parker, from Golden Square and St. Bartholomew's Hos- pitals, are partial to chloroform, it is the general belief that this agent is especially dangerous in lymphatism and should never be used (F. W. Hinkel). The danger is said to be less Avhen it is joined with oxygen. Nitrous oxide gas is universally admitted to carry the least risk, but it is too transient for any but the simplest case. Com- bined with oxygen, its efifect is slightly more prolonged and in other respects it is satisfactory (W. F^. Casselberr}). \\'hen used as a pre- liminary to ether in what is known as the gas-ether sequence, with a Ben- 380 ADENOID VEGETATIONS (KNIGHT AND CARISS). nett inhaler, the process of narcosis is rendered as agreeable, rapid, and safe as possible. By this method a much smaller quantity of ether is needed with proportionate reduction in stimulation of mucous secretion and less of unpleasant after-effect, two of the chief objections to ether. Braden Kyle quotes Royer to the effect that secretion is lessened by adding^ to the ether a few drops of oil of Hungarian pine. The disagreeable odor of ether may l)e partially i)revented by first pouring a little cologne water in the mask, and thus the confidence of a timid patient may be secured. By many operators the "drop" method of giving ether is preferred, especially in young children, and thereby the strain upon the chest walls incident to the use of a closed inhaler is avoided. By some the use of morphine, atropine, or chlo- retone to reduce mucous secretion is advised, but this is not to be recom- mended in the very young. A clear operative held may be procured by means of some form of suction de- vice, now so generally in use. Those who oppose general anes- thesia refuse to admit the fact that the shock without it, especially in a nervous child, overbalances any risk incurred when the plan just outlined is pursued. It is almost indispensa- ble when, as often happens, the palatal tonsils must be removed or other in- strumentation done at the same time. Ethyl bromide and ethyl chloride, the latter said to be the less objec- tionable, have no supreme advantage and are not free from risk. Accord- ing to Lermoyez, the diflficulty in regulating the dose of ethyl chloride, owing to its great volatility, is over- come by giving it with a suitable mask, whereby the quantity inhaled is precisely known. The Apperson inhaler is highly recommended, from 3 to 5 grams of the anesthetic being required for a short operation. The drug is so rapidly eliminated that after-effects are few or absent. Other good features claimed for it by those experienced are ease of administration and rapidity of action. It may be given prior to other anesthetics, or alone continuously for an indefinite time without regard to the position of the patient, upright or prone (G. F. Hawley). At the Royal Infirmary of Edin- burgh, the exi)erience of T. D. Luke has been so gratifying that he rec- ommends ethyl chloride as a matter of routine for short operations. On the other hand Z. Menncll, at St. Thomas's, London, notes the frequent occurrence of pulmonary embolism at that institution since the introduction of ethyl chloride. He attributes it to increased coagulability of the blood caused by the drug, and on this ac- count has abandoned its use. Those who advocate ethyl bromide ascribe disasters with it to the use of an im- pure product, or to the mistake of having substituted for it ethylene bromide. In addition we are enjoined to give it en masse, admitting -no air, and to continue the administration no longer than one minute (A. R. Solen- berger). Most operators will find sixtv seconds too short a time for thorough work. The Schleich inhalation mixture (E. Mayer) and the A, C. E. mixture are urged by some, but have no spe- cial attraction. If the operation is to be done in the upright position, it is customary to give the anesthetic to the patient lying down and to slowly elevate the ADENOID VEGETATIONS (KNIGHT AND CARISS). 381 body when all is ready. Special oper- atinsf chairs have been devised for this purpose (T. R. French). The question of safety being of the first importance, too much stress can- not be laid upon the necessity of choosing- a reliable anesthetic and a trustworthy anesthetist, and ether or nitrous oxide-oxygen ether is the safest and the anesthetic of preference if general anesthesia is used. Insufflation anesthesia, or the forc- ing of ether vapor to the lungs through a tracheal tube (Jackson direct laryngoscope), is pronounced by C. A. Elsberg, of Mount Sinai Hospital, who introduced' the method and devised an excellent apparatus for the purpose, "ideal" in operations in the upper air tract, as regards pre- vention of aspiration of blood and mucous and as to rapidity and safety of narcosis. This view is confirmed by C. H. Peck from experience with a number of cases at Roosevelt Hos- pital. Gas and oxygen passed over anes- thol for the induction of anesthesia, and gas-oxygen-ether to maintain it, are employed by the writer in aden- oid and tonsil work. His equipment consists of an electric heater for warming the anesthetic and a vapor mask with Sanford nasal tubes or a mouth hook and a Whitehead self- retaining mouth gag. Anesthol is placed in one bottle of the ether at- tachment, and ether in the second bottle. The induction is begun with nitrous oxide and oxygen, and after 15 to 30 seconds the anesthol is turned on gradually. In from 1 to 3 minutes the third stage of anesthesia is reached, usually without a strug- gling stage. The ether is then turned on very gradually. When the pa- tient is able to breathe gas-oxygen- ether without coughing or hesitation in breathing, the anesthol is turned off and the anesthesia continued with gas-oxygen-ethcr. Tlic patient's skin remains pink throughout the pro- cedure and there is no rise in blood pressure. In children up to 6 years of age the ether may be turned off very shortly after the operation is begun, the induction of the anesthesia being carried through with gas oxy- gen only, or the gas may be turned off and the anesthesia continued with ether and oxygen. When the aden- oids are being removed the nitrous oxide and the ether are turned off and oxygen is given, the blood being thus in the best possible condition for coagulation. G. T. Gwathmey (N. Y. Med. Jour., c.xi, 1065, 1920). Instruments and Methods. — Chem- ical caustics and the electric cautery have been generally superseded by in- struments for extracting the morbid tissue instead of destroying it and allowing it to slough away. Caustics are available, if ever, only in tractable patients and under guid- ance of the rhinoscopic mirror, the palate being held forward with a re- tractor (White) or by means of elastic ligatures {flexible catheters) passed through the nares and out of the mouth, the nasal and buccal ends being tied or clamped together. Under cocaine the process is not extremely painful. Silver nitrate and chromic acid have been used in this way. Without the utmost care and the use of a guarded applicator there is danger of excessive damage and violent reaction. The electric cautery point or loop is more precise and manageable, but at best these methods are tedious and un- satisfactory. They are reserved for hematophiliacs and those who refuse to be cut. In other cases the cold-wire snare, the guillotine, forceps, and the curette provide a wide choice of cut- ting instruments. A straight snare (Jarvis) may be passed through the naris. or a curved one behind the 382 ADENOID VEGETATJOXS (KXJGHT AND CARISS). velum (Bosworthj. It is successful only when the lymphoid tissue is so bunched in the vault that the wire can readily encircle its base. It is apt to slip and include only superficial portions. The guillotine method, or the com- bined guillotine-curettage, (jr the guillotine-forceps methods are the most commonly used at present. The variations of instruments of all types are numerous, the main features of each t}^pe, however, being similar. The guillotine type in common use is the La Force or some modification, and in the average case, removal of adenoids by this method ])r()ves safe and satisfactory. The early instruments for scraping were the sharp spoons of Justi and of Trautmann. Curettes are now made larger and of different sizes and shapes, and some are pro- vided with forks to catch the resected fragments. Such complicating at- tachments are a disadvantage rather than otherwise. The simpler the in- strument, the easier it is to handle and keep aseptic. While the anesthetic is being given, the patient lies flat on the back. After The instrument of choice is there- upon inserted behind the soft palate and velum, pressed firmly upward and backward into the vault of the pharynx and, if the guillotine type is used, the blade is forced shut and the adeno- White's palate retractor. the muscles are somewhat relaxed, a mouth-gag is inserted. If the palatal tonsils are enlarged, they are first re- moved. A little more anesthetic may now be required. The nasopharynx is explored with the finger to deter- mine the extent and distribution of the growths. Schuetz-Gradle adenotome. tome removed with a sweeping motion. Digital examination of the pharyngeal vault following removal of the main mass of adenoid tissue by this means may disclose small shreds remaining, especially in the region of Rosenmuel- ler's fossae, and these may be removed by some form of curette or forceps, as the individual operator prefers. By many a curette of the Gott- stein or Beckmann pattern is used for the whole operation. A curette of proper shape and size, and correctly used, certainly sweeps off the tissue most effectually. The blade, always quite sharp, is slipped behind the velum and crowded from below up- ward close to the posterior margin of the vomer, and then by a quick move- ment pushed backward and slightly downward through the base of the growth. A clean, complete removal is thus ensured, at least as to the vault itself, when the conformation of the region is normal. Unless the ADEXOTD VEGETATIOXS (KXIGHT AND CARTSS). 383 blade is passed close to the posterior surface of the velum and is made to hug" the vomer in its upward move- ment, pendent masses are apt to be crowded into the choanse. By giving the shaft of the curette a curved or bayonet shape it is possible to avoid the obstacle offered by the incisor teeth or by the palate and thus reach far- ther forward in the vault (J. Fein). part is apt to remain vulnerable for some time, often highly sensitive to atmospheric changes, so that the at- tacks may not altogether cease until steps have been taken to brace up the relaxed mucous membrane and re- duce its susceptibility to chills. It is, therefore, advisable to remove the patient, soon after the operation, to the seaside, choosing a situation which is moderately bracing, but not bleak. He should be taught to breathe as much as possible through the nose, and should pass the greater Denhard's mouth grag. Other curettes are made heart- shaped, so as to actually enter the nares on either side of the septum (C. E. Hunger). The nasal route for reaching ade- noids has been revived by Freer, who part of his time in the open air. There are two applications which are very serviceable in these cases. Twice a day a solution of resorcin in normal saline (5 or 10 grains to the ounce, with the addition of half a dram of tincture of hamamelis) should be in- Brandegree's adenoid forceps. recommends for the purpose a modi- fication of Ingal's straight nasal cut- ting forceps. The blades are directed by the finger passed behind the velum, and in any case it is a useful instrument for clearing out the post- nasal arches, where fragments are sometimes missed and afterward give trouble. Even when the postnasal adenoids have been completely extirpated, the stilled into the nostrils as the child lies on his back with his head sup- ported by a pillow. Five or six drops may be used to each nostril with a "dropper," allowing the fluid to trickle down into the pharynx. After using these drops for a week we can begin to paint the pharj-nx. The best ap- plication for this purpose is a solution of 15 grains of potassium iodide and 12 of iodine in an ounce of water, well sweetened with glycerin. This should be applied twice a day to the 384 ADENOID VEGETATIONS (KNIGHT AND CARiSS). pharynx with a brusli, taking care to sweep the brush round with a turn of the wrist before withdrawing it, so as to reach as high up as possible behind the soft palate. This applica- tion not only checks morbid over- secretion by curing the nasopharyn- geal catarrh, but also puts an end to laryngeal irritation and favorably in- fluences the glandular enlargement. In fact, this is the very best method treatment does cause shrinkajre of tonsils and adenoids and an in- creased fibrosis and an atrophy of the lymphoid constituents of these struc- tures, but whether the diseased pro- cess is arrested — and this and not size is the usual indication for treatment or removal — reinains to be proven, in view of the diverg'ence of opinion. Knight's adenoid forceps. of treatment for acutelj^ swollen cer- vical glands, and as long as the latter remain of elastic softness, varying in size from time to time according to the amount of laryngeal worry, we may expect them to be dissipated by this means. Smith (Practitioner, Jan., 1910). Recently, much has been done and much has been reported rejjarding' the treatment of diseased tonsils and adenoids by means of X-ray and radium. The author's experience has been that but little, if any, change has been pro- duced in the diseased condition and operation has been necessary in many cases which have previously been ex- posed to X-ray or radium treatment. The chances of recurrence in the ordinary case diminish rapidly from the age of 4 to 7 after which they are practically nil, unless anterior nasal obstruction exists or measles or whooping-cough supervenes. T, Guthrie (Lancet, Apr. 20, 1912). Gottstein's adenoid curette. Many of the adherents of these methods have made claiins of remark- able results and have advocated treat- ment by such means instead of surg- ical removal. The opinions of the writers for and against this method are so divergent and so numerous that the conclusion must be reached that these methods of treatment are still on trial. Undoubtedly X-ray or radium Accidents and Complications. — The most serious accident is hemorrhage, which may be first shown by pallor and rapid, flickering pulse. Small children should be closely watched and not allowed to sleep continuously for sev- eral hours after operation. The con- trast between the quiet and the pre- viously noisy breathing often creates enough anxiety to enforce this cau- tion. Bleeding usually ceases spon- ADENOID VEGETATIONS (KNIGHT AND CARISS). 385 taneously in a very few minutes. The total loss of blood is ditificult to esti- mate; according to C. G. Coakley, from 2 to 8 ounces is the ordinary quantity. If in excess or too long continued, measures to check it must be adopted. Operations upon the pharyngeal tonsils are generally considered with- out danger, yet wound infection and hemorrhage, although comparatively rare, do occur frequently enough to warrant careful attention. Hemor- rhages may be divided into 2 types: those appearing at the time of opera- tion, and those occurring some time afterward. In the first instance the causes lie in a constitutional or a local condi- tion, the most important of which is hemophilia. This is shown by family and personal history. If there exists absolute proof of a hemophilia, naturally the operation would be de- nied. But in such cases as appear relatively doubtful the operation should be given the benefit of the do.ubt. An unrecognized leukemia can be the cause of excessive hemor- rhage. Characteristic is the livid bleached color of the tonsils. Opera- tion in such cases can produce the same untoward results as in hemo- philia. Among other diseases which impose the danger of severe post- operative hemorrhage are nephritis, heart lesions, etc., which, however, appear so rarely in cases needing adenoidectomy that tlvey can be neglected. Many authors have associated se- vere postoperative hemorrhage with the coincidence of the operation and menstruation. About 1 per cent, of cases have postoperative hemorrhage. Injury to neighboring parts, and es- pecially the leaving of partly removed tissue shreds, are the important fac- tors. The former more often leads to hemorrhage immediately following the operation, and only to after- bleeding when the blood-clot cover- ing the lesion is accidentally removed. 1—25 Mucous membrane shreds hanging from the wound are found in over 50 per cent, of after-hemorrhages. Hemorrhages occurring after several days generally follow sudden muscu- lar exertion, such as sneezing, blow- ing the nose, etc., and are due to dis- location of the exudate covering the wounded surface. Healing had pro- gressed so far after a week's time that bleeding is no longer to be feared. Haymann (Archiv f. Laryngologie, Bd. xxi, S. 15, 1908-1909). Reference has already been made to the internal use of calcium chloride or lactate in hemophilia, and many local applications are advocated such as thromboplastin, hemoplastin, coag- ulen, and thrombokinase. Locally, in- stillations of adrenalin chloride, 1 to 1000, are sometimes effective. Direct pressure by means of a gauze tampon crowded up into the vault in the grasp of a postnasal forceps is usually successful. At times it may be neces- sary to retain the postnasal gauze tampon In sifit for several hours, hav- ing pulled it up firmly in the vault of pharynx by means of tape through nostril and securing tape externally by means of adhesive plaster. The gauze may be soaked in a saturated solution of tannogallic acid ( 1 part gallic, 3 parts tannic), one of the clean- est and most active hemostatics. Signs of collapse are to be combated by saline injections, stimulants, con- stricting the extremities, and similar expedients. Even after extreme ex- sanguination the repair of waste is generally rapid, but may need to be encouraged by the use of ferruginous tonics or other medication. Such being the case, the proposal of Iglauer to transform adenectomy into an "almost bloodless" operation by packing the postnasal space with a tampon of rubber sponge the moment 386 ADENOID VEGETATIONS (KNIGHT AND CARISS). the adenoid mass has been removed is of doubtful utility. The plan suggested is like that fol- lowed in plugging the posterior nares for epistaxis. The tampon is ready before the operation is begun, and the tai)e at- tached to it is used as a palate re- tractor during instrumentation. The handle of the forceps cutting laterally should not be too much de- pressed lest the margin of the vomer be nipped between the blades. Care should be taken to keej) the blade of a cutting- instrument in the middle line of the vault : if tilted to one side, there is danger of harm to the luista- chian cushion. A rare and interesting complication, torticollis, has been described l)y sev- eral writers and is probably due to sepsis or to excessive energy in the use of instruments. It disappears spontaneously in a few days and is worthy of note only because of the unnecessary alarm to which it may give rise. Laceration of the velum would seem to be inexcusable, but has been known to occur with rough handling of an ex- cessively large instrument, or from at- tempting to make use of a cutting edge in a struggling child, or before one is quite sure that the instrument has passed beyond the plane of the velum and is well within the cavity of the Jiasopharynx. Finally, the mucous membrane may be stripped up over an excessive area, if too dull an instru- ment be us.ed, or if it be forced too deeply into the tissues. With the ex- ception of the first-mentioned, hemor- rhage, these accidents are obviously all unfortunate results of faulty ma- nipulation. Reports of deaths from pulmonary abscess following operative proced- ures of the upper respiratory tract have been increasingly numerous and have stimulated investigation of this complication, and have added many adherents to the view held by too few, unfortunately, that operations in this area are not to be seriously consid- ered. There is still a wide divergence of opinion as to whether the condition is a result of blood stream infection, of lymph channel transmission, or of direct inspiraton during operation, and each investigator holds his own view regarding the means of produc- tion and of the methods and the ap- pliances for possible prevention of this complication. Attention has been called by Wyatt Wingrave and others to a peculiar transitory rash resembling that of scar- latina at times following removal of adenoids or tonsils. It merits notice only for the danger that it might be confounded with a more serious infec- tious exanthema. No precise theory of the phenomenon is propounded, whether septic or nervous, although marked leucocytosis is demonstrable for a week or ten days after. Several cases of alleged sepsis have been recorded, but in many the histories are by no means conclusive. A case of fatal meningitis, believed to be septic, has been reported by Shurly ; two similar cases have been noted by Putnam, who expresses the opinion that such sequelse are not un- common. An interesting case of cav- ernous sinus thrombosis in which the surface of the basilar process of the occipital bone had been shaved off together with an adenoid mass with a Beckmann curette is a graphic warning" against the use of extraordinary force (A. E. A\'ales). Cases of pharyngeal ADENOID VEGETATIONS (KNIGHT AND CARISS). 387 abscess, inflammation of the cervical glands, endocarditis, and acute rheuma- tism have been met with by various observers after adenectomy. Several instances of lighting up of latent tuberculosis by adenectomy have been reported (Lermoyez, Chappell). It is perhaps more correct to say that tubercle bacilli lying in the operative field have ready admission to the cir- culation through the divided lymph- channels, whence general infection fol- lows. In the majority of cases the adenoid tuberculosis is undoubtedly secondary to a focus in the lung or else- where which is excited to activity by the surgical shock of operation. In a primary case the results of removal are favorable (E. H. White), but there must always be difficulty in deciding this question of priority. In the development of pulmonary tu- berculosis adenoids may sometimes be direct channels of infection, but their importance is probably more often in- direct by predisposing to catarrhal in- flammations of the upper respiratory tract. E. Hamilton White (Amer. Jour. Med. Sci., Aug., p. 228, 1907). The writer f.ound evidences of tu- berculosis in the growths in only 1 of 27 cases of adenoid vegetation, and in this case it was evidently second- ary. Wikner (Hygieia, April, 1910). An interesting case is mentioned by J. L. Morse, in which "adenoids were removed from an infant of five months during the early stage of tuberculous meningitis, tubercle bacilli being found in the adenoid tissue," The possibility of infection by this route is looked upon as a strong reason for operating in the early months of life, even with the certainty that a repetition will be called for at a later period. Spasm of the glottis requiring tra- cheotomy, as in cases of his own, is believed by Holger Mygind to be not infrequent in adenectomy without an- esthesia in rachitic children, and one should be prepared for such an emer- gency. The writer has twice witnessed seri- ous disturbance of respiration (laryn- gospasm with stridulous inspiration and marked cyanosis of the lips) as a result of adenotomy without use of chloro- form. Both cases were children under 2 years having symptoms of rachi- tis. In the third case, in a boy of 2 years, with rachitic deformities, there was sudden collapse accompanied with suspension of respiration and cyanosis consequent to adenotomy, which re- quired tracheotomy. The child's mother later declared that the child was subject to fits of suspension of respiration with cyanosis. On two occasions he had such attacks in the presence of the family- doctor, and artificial respiration had to be em- ployed. Holger Mygind (Hospital- stidende, Nov. 18, p. 1173, 1903). Case in which a very large adenoid removed from a child aged 6 years gave rise to asphyxia on spasmodic closure of the jaw just as the child was appar- ently under complete ether anesthesia. The writer had to resort to artificial respiration, hypodermic injections, forcible opening of the jaw, and traction of the tongue in order to re- suscitate his patient. G. L. Richards (Laryngoscope, Feb., p. 289, 1905), After-treatment, — The control of hemorrhage, and that in very excep- tional cases, is practically the only indication for interference during con- valescence. If catarrhal secretion is overabundant, it is sometimes desirable to keep the parts clean with a douche or coarse spray of warm normal salt solution. Drainage from this region is so good that sepsis is almost unknown, and it is well to abstain from the use of antiseptics, either in solution or powder. In order to prevent the formation of adhesions, the passage of the finger into the vault for a few days after 388 ADIPOSIS DOLOROSA (DERCUM). operation has been recommended. Al- though no statistics on this point are available, it is believed that adventitious bands met with in adult life are due not to operative interference, but to at- trition and erosion of lymphoid masses in childhood which have been neglected and have finally undergone spontaneous shrinkage. Removal of adenoid vegetation has l)rouglit aKoiit, in tiie writer's hands, recovery of 2 cases of exophthal- mic goiter, 1 of glaucoma due to lesion of the fifth pair and not re- lieved by iridectomy, and of 1 case of Addison's disease. The persistence of the craniopharyngeal canal and an accessory pituitary gland encountered sometimes in the pharynx, might cause an alteration in the secretory function of the pituitary body, and the sympathetic nerve, through the other glands of internal secretion. Popp (Annales des mal. de I'oreille, du larynx, etc., Oct., 1909). The pharynx, as a rule, is relatively small in children with adenoids, sometimes interfering with respira- tion, deglutition, and clear speech after the adenoids have been re- moved. It is possible in such cases to develop and broaden the bony pharyngeal walls by exercises of the pterygoid muscles, viz., lateral, ver- ticle and anteroposterior movements of the lower jaw, made against re- sistance ofTered by the hand of an instructor who holds the jaw firmly. F. Warner (Lancet, Dec. 20, 1913). No procedure in the upper air tract has added so much to the vigor of the race as removal of adenoid vege- tations, and the fact must be admit- ted that they are often a source of disease, even when their volume is not sufficient to cause obstructive symptoms. ,^ tt t^ ■' ^ Charles H. Knight, New York AND Walter L. Cariss, Philadelphia. ADIPOSIS. See Obesity. ADIPOSIS DOLOROSA; DER- CUM'S DISEASE. [The term "Dercum's disease" is that by which adiposis dolorosa is generally known in Europe. Hence its introduction here l)y the Editors.] DEFINITION.— Adiposis dolorosa derives its name from its two principal features, namely, fat and pain. [Objection may naturally be made to the form of the word "adiposis," as it is of mixed origin, being made up of a Latin root joined to a Greek termination. It has, however, the sanction of generations of use among English-speaking writers, and, besides, is paralleled by other mon- grel words in common use, such as term- inology, which no one any longer ques- tions. The correct Latin form of the word would, of course, be "adipositas," the word used by German writers. How- ever, adipositas is equally a coined word, a word artificially made, for it is not used by any Latin writer. The real Latin word is "obesitas," which, as purists, we ought to use. V. X. Dercum.] In 1888, the writer described the symptoms which constitute this affec- tion in reporting a case under the title of a subcutaneous connective-tissue dystrophy. Later, in- 1892. he grouped this case, a second described by F. P. Henry, and a third discovered in the wards of the Philadelphia General Hos- jMtal under the name "adiposis dolo- rosa," by which the afifection has since become generally known. Within the next few years cases were published by Collins, Peterson, Ewald, Eshner, Spil- ler, Fere, and others. In 190L Louis Vitaut (Those de Lyon. 1901, "Maladie de Dercum") published a special treat- ise on the subject. His description of the afifection was so full and accurate that at the present date it needs but lit- tle modification and but few additions; the latter mainly bear upon the pathol- ogy of the afifection. Up to the present ADIPOSIS DOLOROSA (DERCUM). 589 time between 50 and 60 cases have been recorded. [Among the more im- portant papers upon the subject are those of Frankenheimer (Jour. Amer. Med. Ass'n, 1908, i, p. 1012), of Price (Amer. Jour. Med. Sci., May, 1909), and the thesis of Poirier, ]\Iontpeher, 1910.] SYMPTOMS AND COURSE.— The development of the disease is usu- ally slow and insidious. A woman who, up to the period of onset, has been well and occupied with her usual occu- pation notices a slight pain or tender- ness in this or that portion of the body. This early symptom of pain is very variable in character and in intensity. Most often it is a sensation of smarting or stinging more or less annoying be- cause of its persistence. Sometimes the pain, even in the beginning, is severe, though this is unusual. At other times the onset of symptoms is preceded by a sensation of cold in regions in which pain subsequently makes its appearance. As a rule, the pains at first are not very pronounced and the patient is for some time able to follow her ordinary occu- pation. Furthermore, the pains are not persistent, but recur at intervals, the patient being comfortable for hours and sometimes for days at a time. Little by little the pains become more pro- nounced, they increase in intensity and are then also accompanied by distinct local changes. The patient naturally examines the part which is painful and may note these changes herself. Some- times there is a little flushing of the skin and sooner or later a swelling is noted. At first it is hardly appre- ciable, but gradually becomes more pro- nounced. The swelling may give a sensation to the finger of a rather firm localized edema. As a rule, it is in the beginning a small nodule, — smaller than a walnut, rarely larger. Sometimes a number of such swellings are noted at the same time. The aflfection continues to evolve, usually slowly ; the pains be- come more intense and more frequent, and gradually the tumefactions change their character and finally become veri- table tumors or great tumor masses. In rare cases the fatty deposit appears to make its appearance without either previous or concomitant pain, the pain making its appearance only after the enlargements or swellings have existed for some time. This, as already stated, is unusual, the most common history by far being that just outlined. The pain is quite commonly paroxys- mal, though in long-established cases it may be continuous. In the intervals the tumefactions are usually tender or pain- ful to pressure. When the disease is well established, we may distinguish, as pointed out by \ itaut, 4 cardinal symptoms, namely, tumor formations, pain, asthenia, and psychic symptoms. The swellings may present themselves under three different aspects. Some- times they are small, of variable dimen- sions, distinct from one another, and readily isolated. Under these circum- stances they present what Vitaut has termed the nodular form of the disease. Sometimes they form extensive masses, invading an entire limb or the segment of a limb. To this condition A^itaut has given the name of "localized diffuse form." Finally, a tumor, properly speaking, may not be present, but the entire body may be augmented in vol- ume in consequence of a hyperplasia of the fatty subconnective tissue. This con- dition Vitaut has called "the general- ized diffuse form." The Nodular Form. — The nodular form manifests itself at first by pains. 390 ADIPOSIS DOLOROSA (DERCUM). variable in character, stinging, itching, changes, so that it no longer has the smarting, shooting, soon followed by a appearance of a simple tumefaction, but slight redness of the skin and a slight that of an actual tumor. Each increase induration scarcely appreciable to the of swelling is preceded or attended by finger. If we examine the painful area, characteristic pains. The latter are we feel a tumefaction, usually of small sometimes so sudden in their onset and ,r^%i^ ^iss: ^:i: ^Li^msm^ Author's first case (Dercum.) size, at first yielding and later a little more resistant. The sensation is that of a firm edema, which is not well differ- entiated from the surrounding tissue. The tumefaction appears to develop slowly in keeping with successive at- tacks or crises of pain. Gradually it becomes somewhat better defined, its volume increases, and its consistence so severe as to cause the patient to cry out. During the height of the paroxysm, the tumor may resemble very closely, in the sensation which it gives to the fingers, a "caking breast." The painful crisis having passed, it is found that the dimensions of the swell- ing have distinctly increased. It has become permanently larger, as well ADIPOSIS DOLOROSA (DERCUM). 391 as more resistant and better defined, capsulated. Sometimes after a crisis After repeated paroxysms, the swelling we discover around the tumor a well- resembles a distinct tumor more and defined edematous zone, which in sub- more closely. In certain portions, the sequent crises undergoes a transforma- mass may appear finely lobulated, while tion such as the original mass itself had in other parts it gives to the fingers the undergone. In this way the mass may Case of adiposis dolorosa in a male. (Dercum.) sensation of a bag of worms beneath the skin. Each painful crisis leaves be- hind it very appreciable changes. In an area where nothing existed pre- viously, we find after a crisis a diffuse edematous tumefaction: if the tume- faction has existed previous to the crisis, we find it transformed into a lobulated tumor more or less well en- eventually attain great size. The vari- ous stages of the evolution of these masses can be followed very closely by palpation. One and the same patient, besides, usually presents in various regions tumors in various stages of development. Painful crises supervene usually with- out appreciable cause ; at times they are 392 ADIPOSIS DOLOROSA (DERCUM). provoked by trauma and at others they ensue upon unusual exertion. The pa- tient is frequently very positive in stating that slight contusions of the surface or that excessive fatigue pro- vokes the painful crises. The tumors are, of course, variable in size. Some of the very smallest may be no larger than a pea, though so small a mass is the exception. More frequently the mass is of the size of a walnut or a small orange. Much larger sizes are met with. The larger masses are of course evident to ordi- nary visual inspection ; the smaller ones require to be sought for by palpation. If we examine the patient attentively in a good light, we are struck by the changes in the skin in certain areas. In ])laccs, indeed, it presents a bluish tint due to a slight superficial veining, and if we examine such a region by the feel we frequently discover a small subjacent tumor. Small as the tumor may be, it may betray its existence by this bluish tint in the skin which covers it. It hapi)ens sometimes that these small tumors become confluent and finally form a single large mass. Such a mass gives rise to a sensation like that of a varicocele or of a bag of worms. The masses do not appear to have a special localization ; they are sometimes symmetrical in the beginning, but soon group themselves without any apparent order. They develoj) by preference over the limbs or in the segments of a limb. In some patients it is limited to the arms and thighs, or forearms and legs in others. Sometimes we find them on the tliorax, abdomen, and lumbo- sacral region. The face, hands, and feet are never involved. The relations of these neoplasms to the surrounding tissue- vary according to the degree of their development. In the state of edematous swelling, they pass without exact limitation into the surrounding tissue. The skin is but slightly movable over them. Later, when they form distinct tumors, more or less encapsulated, they are mobile in all directions and the skin which covers them may be folded above them. How- ever, they are slightly adherent to the latter, so that if one tries to displace the superjacent skin the movement is trans- mitted to the underlying tumor. Fi- nally it may be noted that these masses are painful not only during the crises, but are very tender to pressure, and this tenderness, as already pointed out, may ])ersist in the intervals between the paroxysms. The Localized Diffuse Form. — The localized dififuse form may present it- self primarily or it may develop out of the nodidar form. When it develops from the nodular form, it is because the nodules multiply so rapidly that they unite and become confluent. In this way a more or less voluminous mass may develop, which involves a portion of a limb or it may be a segment of a limb or even an entire limb. However, this is not the usual method of origin of the localized diffuse form. In the nodular form the separate masses are generally so small and the evolution so slow that the patient has usually been under observation for some time before the masses become confluent. More frequently the localized dififuse form originates spontaneously and rapidly in an entire limb or a segment of a limb. In such a case the pains are felt over a correspondingly extensive region. At first the entire region presents an edematous swelling easily observable by the eye. Subsequently the evolution of the mass is substantially the same as in the nodular form. Painful crises are ADIPOSIS DOLOROSA (DERCUM). 393 here again present and the swelhng in- creases in size with each successive attack. Finally, a mass is formed which is resistant and painful to pressure. It may be quite smooth or it may be finely lobulated, or separate, apparently en- capsulated tumors may be found im- bedded in the general lipomatous mass. Naturally, in the localized diffuse form it is difficult to make out the limitations as clearly as in the nodular form. The masses involve more espe- cially the limbs, excluding save in the rarest instances the hands, the feet, and the face ; not rarely they are found on the thighs and on the back. The tume- faction may be excessively painful and may present during a crisis the sensa- tion given by a breast distended by milk or, to repeat a term already used, a "caked breast." The Generalized Diffuse Form. — The generalized diffuse form is much less characteristic than the nodular or the localized diffuse form. The origin and course of the affection is, however, the same. The edema may appear rapidly, even suddenly, over the greater part of the surface of the body and limbs, exclusive again of the face, hands, and feet. It increases progress- ively and produces a general lipoma- tosis. More frequently it begins in a certain part, such as the abdomen, some- times upon one side, and then diffuses itself gradually over neighboring por- tions of the trunk and limbs. Other masses may make their appearance at the same time or subsequently, and, be- coming confluent with the original mass and each other, a diffuse lipomatosis results. The regions affected are ordi- narily the arms, the chest, the abdomen, the hips, and the thighs. Contrary to the case in the nodular and localized diffuse forms, the hands and feet are not always in this form absolutely free. At an advanced stage of the disease, it is not unusual to see small masses of lipomatous tissue over the thenar and hypothenar eminences and even on the soles of the feet. In one case the writer observed even a slight invasion of the face. Only the back of the hands and the backs of the feet escape invariably the lipomatous invasion. In consistence the swelling is resistant, but much less so than in the nodular form. The mass is spontaneously painful and tender to pressure. Sometimes the suffering owing to the universal tender- ness is very great. Occasionally it is such as to prevent movement on the part of the patient and to immobilize him in his bed. Of the three forms the most common is the nodular. It presents a special physiognomy, which makes its recogni- tion easy. The localized diffuse form resembles certain forms of ordinary lipomatosis, but it is, notwithstanding, differentiated by the pain and other characteristics still to be considered. The pains are never absent. They are present either spontaneously or are readily elicited by pressure. Usually they manifest themselves in both of these ways. Most often they pre- cede the appearance of the edematous swelling. Sometimes they come on at the same time as the swelling; more rarely they are not noted until after the swelling has made its appearance. Slightly marked and intermittent, they become more violent when the disease is established. The pains are described by the patients as stinging, burning, pinching, darting, or even lancinating. Most commonly they are darting and radiate or diffuse in and about the nodules. They do not follow the large nerve trunks or indeed any nerves. 394 ADIPOSIS DOLOROSA (DERCUM). The patient describes them as though they were situated in the thickness of the masses. The muscles, the bones, and joints are not painful. The pains are exaggerated or brought on by pres- sure or handling. If the fatty accumu- lation is considerable, movement and effort may increase the pain to such an extent that the patient may be obliged to remain perfectly quiet during the paroxysm or indeed continuously. There is one characteristic which one finds in all cases, namely, the parox- ysmal exacerbations already described. vSuddenly and without cause or follow- ing an effort or trauma the patient again feels active jiain. At the same time the new formations increase in volume; if it concerns a nodule the latter is surrounded by an edematous zone more or less extended; if it is a case of diffuse swelling the skin in this region becomes more tense and the cir- cumference of the mass increases. As the pain subsides, the swelling recedes, but never to its former dimensions. After each crisis, the volume of the new formation is increased. All or almost all of the patients pre- sent the symptoms of a general asthe- nia. The patient is very readily ex- hausted. Even in cases in which the muscular development is good, this fact is early noted. In cases which are ad- vanced the asthenia is very pronounced. Sometimes this is so marked that the patient is unable to leave the bed. Sometimes she is unal)le to change even her position in bed largely because of her weakness, but also because of the pain and the enormous increase in the size and the weight of the limbs and body generally. The psychic symptoms are not con- stant. However, they are very fre- quently present. A cerebral asthenia or ready cerebral exhaustion is rarely absent. Many patients present in addi- tion great irritability; this is at times so great as to be attended by a change in character and disposition. The least opposition may enrage the ])atient and not infrequently she will quarrel with her neighbors in the wards to such an extent that isolation becomes impera- tive. Sometimes she thinks that the other patients and the nurses are against her. 'Ilie sleep is usually broken and disturbed by distressing dreams and nightmares. One of Eshner's pa- tients was disturbed mentally to such extent as to necessitate her commit- ment to an asylum. Male White's case had two attacks of mental dis- turbance. Ciiudiceandrea has noted delusions of persecution and a true dementia. In several cases lessened sensibility to touch, pain, and temperature have been noted. In the writer's first case there were found areas of anesthesia, while in other areas the sensibility was diminished. The same patient com- plained of velvety sensations in the finger tips and in the soles of the feet. The case reported by Henry pre- sented marked disturbances of sensa- tion. Touch, i)ain, and temperature were sometimes not perceived ; at other times confused. In Giudiceandrea's case the sensi])ility to pain, on the other liand, was much increased, especially in the regions corresponding to the adi- posed masses. The thermal sensibility, again, was particularly exquisite in the regions in which there was no trace of the neoplasms. Hyperalgesia was noted by Achard and Laubry. Patients have also complained of sudden sensa- tions of cold or heat, of formication, or of cramps in various parts of the body. Headache is not rare. ADIPOSIS DOLOROSA (DERCUM). 395 Disturbances of the special senses are quite frequent. In some observa- tions there was noted a narrowing- of the visual fields ; in others various subjective sensations, such as phos- phenes, musc?e volitantes ; in one case amaurosis was noted, which began to disappear from the day that thyroid treatment was instituted, and in a case of the writer there was present a circinate retinitis, — a mass of partly fibrinous and hemorrhagic exudate in the center of the retina, surrounded by crescents of fatty degeneration in Mueller's fibers. Diminution of auditory perception has been noted several times. In some cases tirmitus more or less marked has been recorded. Smell and taste were impaired in one of the writer's cases. Vasomotor disturbances have been very frequently noted. The skin over a nodule may present no changes whatever; on the otlier hand, it may be noted to be somewhat injected during a crisis of pain, or much veined and slightly bluish. Occasionally the face is much flushed, — the malar re- gions, the frontal regions — or it may be the neck, although no actual indura- tion or swelling accompanies the change in color. In some cases cyanosis of the ex- tremities and transitory edema have been noted. Frequently also the patient notices that his flesh bruises very readily, and it is not uncommon to note small ecchymoses on various portions of the limbs and trunk, and at times these evidently make their appearance spontaneously and inde- pendently of trauma. Perhaps, in keeping with this fact is the history, not infrequently obtained, of excessive menstruation or even of metror- rhagia. At times also epistaxis and, in one of the writer's cases, even hematemesis are noted. Trophic changes in the form of ulcerations, blebs, and bullae have been observed. It is important also to add that tliere is quite commonly a marked dryness of the skin. Patients them- selves comment upon this and ex- amination confirms it. Adiposis dolorosa with involvement Of the joints. (Dercum.) Among unusual complications noted in adiposis dolorosa are changes in the joints. Attention was first directed to this by Renon and Heitz, who in 1901 presented a case of "adiposis dolo- rosa with multiple arthropathies," be- fore the Neurological Society of Paris. In addition to the usual symptoms of the aft'ection there were present marked pain, creaking, and limitation of move- ment in numerous joints. A skiagraph of the left knee failed to reveal any alteration of the articular surface. The knee-cap, however, was a little thick- ened, and its structure offered a some- what mottled appearance. The syno- vial membranes gave rise to a slightly opaque shadow, which was especially evident at the cid-dc-sac under the 396 ADIPOSIS DOLOROSA (DERCUM). quadriceps tendon. This shadow, In- froit, who made the skiagraph, re- garded as due to fatty thickening of the synovial membrane. In 1902 the writer placed on record (Philadelphia Medical Journal, Decem- ber 20th) a second case of adi- posis dolorosa with involv^ement of the joints. Skiagraphs revealed no changes whatever in the bones, but some thickening of the tissues about the joints, especially about the knee- joints. The conclusion was justified that there was present a marked thickening of the synovial membranes and possibly of other structures in the neighborhood of the joints. There was a marked tendency to the forma- tion of fringes and rice bodies. The joints appeared, as the patient ex- pressed it, to be "loose," and motion was attended by considerable pain. Iliat the changes ob.served were due, in part at least, to fatty infiltration, and that this fat was painful, just as was the fat in the tumor masses on the surface of the body, afforded the most reasonable explanation of the condition. It was possible also that an actual synovitis was present. Rheumatism could not ofTer an ade- quate explanation of the conditions found, while rheumat'oid arthritis was excluded l)y tlic absence of changes in the bones and cartilages. More recently Price has made studies in the joints of two other cases con- firming these findings. A most interesting case of adiposis dolorosa in which bony changes were noted in the dorsal vertebrae and in the ribs has been placed on record by Price and Fludson (Journal Nervous and Mental Diseases. April 19, 1909). Kyphoses with corresponding de- formitv and reduction in size of the vertebrae were noted in the dorsal region and confirmed by the skia- graph. Similar changes were noted in the ribs. The authors call atten- tion to the possible significance of these findings w^hen the frequency of pituitary changes in adiposis dolorosa is borne in mind. The course of adiposis dolorosa is essentially chronic. Its progress is slow, the patient being worse or better by turns in accordance with occurrence of paroxysms of pain. In well-established cases the suffering is continuous, subject always to more or less marked exacerbations. In the majority of cases tlie patients become extremely obese, the weight often running from 200 to 300 pounds ; in others again, in the nodular form, the w^eight may undergo only a moderate if any increase. The symptoms may be briefly sum- marized as follows : fatty deposit, pain, general asthenia, and psychic symptoms. The deposits are present either in the nodular, a localized dif- fused or a generalized dift'used form. The distinction between these, forms is of course not absolute, as combina- tions of the various forms — or transi- tional states — may be found in one and the same patient. The deposits are found most commonly over the trunk, shoulders, arms, and thighs; the forearms and legs being less fre- quently afl^ected and the hands and face almost never. Pain and tender- ness upon manipulation of the swell- ings are present ; spontaneous pain, j)ain occurring in paroxysms, is also present unless it happens that the patient is observed during an interval between paroxysms. Involve- ment of the nerve trunks is rare, though it has been a few times observed, not- ADIPOSIS DOLOROSA (DERCUM). 397 ably in a case of Bergerson's. Anes- thesias are rare, hypesthesias not un- common, paresthesias are frequent ; the latter consist, as already pointed out, of sensations of numbness, cold, burning, tingling, crawlmg. The general asthenia and the mental phenomena have been already sufficiently considered. The tendon reflexes may be normal or increased, but are usually dimin- ished and sometimes abolished. In one case, that of Delecq, the skin reflexes were lost. Coincident gross nervous disease has been noted several times. Hemiplegia and apha- sia were noted in one case ; in another, a case of the writer, a sclerosis of the columns of Goll was revealed at the autopsy, and in still another there was involvement of the lateral tracts. ETIOLOGY. — It is occasionally noted that the patient presents a neuro- pathic heredity; not infrequently grave nervous disorders are noted among the ancestors or collateral relatives. Now and then it is noted that other members of the family are unusually stout, e.g., in 1 of Eshner's cases the mother was obese. In a few instances adiposis dolorosa has been observed in members of the same family. Thus, Cheevers reported the case of a man whose father and sister both had the dis- ease, while Hammond reported 2 cases occurring among sisters. The striking fact in the etiology is the predominance of the female sex ; the ratio is about 6 women to 1 man. The age at which the disease makes its appearance is exceedingly variable. The youngest re- corded case, that of Hale White, began at 12 years of age; the oldest case recorded was 78 years of age. Ac- cording to Frankenheimer, the major- ity of cases in men occur between 30 and 40 years of age, and in women between 30 and 50 years. The disease was originally believed to occur exclusively in women and about the climacteric period ; although this was the rule in the writer's experi- ence, he has known it to begin as early as 12, and has seen 3 cases in males. He describes in detail 5 cases of the aflfection, 4 in women whose ages range from 20 to 42, and 1 in a man aged 47. These cases all presented the char- acteristic symptoms of the disease. The panniculus adiposus was invariably thickened, sometimes to a marked ex- tent. The skin was red and in depend- ent parts has a bluish, livid appearance. It was painful, sometimes with a feel- ing of burning, at other times as if it were being pierced by a needle. The skin of the legs especially, but occasion- ally that of the trunk and arms also, was thick and infiltrated, generally in patches, but in some cases in large areas involving the whole lower extremity except the feet. The latter condition is described by the writer as "elephan- tiasic edema." Actual edema was not present, the skin did not pit on pressure, and no fluid was obtained on punctur- ing with a needle. Charcot observed this condition in connection with indi- viduals suffering from functional dis- turbances of the nervous system, and named it "cedeme hysterique." Strub- ing (Archiv f. Dermat. u. Syphil., Feb., 1902). Case of adiposis dolorosa, or Der- cum's disease, believed to be unique, in a newborn infant. The writer was called in consultation to see the child on the day after its birth. It was then 5 weeks old, and, in addition to the characteristic irregular symmetrical de- posits of fat, which were situated on the upper half of the body (the lower extremities being normal), there were two cystic formations of considerable size, one on the left posterior aspect of the neck and the other on the left breast. While lying undisturbed the child appeared to be entirely comfort- able, but the slightest movement was attended with pain. W. C. Walser 398 ADIPOSIS DOLOROSA (DERCUM). (Boston Med. and Surg. Jour., June 30, 1910). Occasionally the patient presents a history of antecedent alcoholism or of syphilis. As Price says, the toxic ef- fects of alcoholism and syphilis are well known and the fact that they frequently cause degenerative changes in the duct- less glands has been emphasized l)y Lorand. This is suggestive when we learn of the role which the ductless glands appear to play in adiposis dolo- rosa. In a case described by E. W. Taylor, the disease developed while the patient was convalescing from an acute alcoholic neuritis. In quite a number of cases excessive menstrual How and even uterine hemorrhages have been noted. In one case, that of Spiller, the adiposis dolorosa followed pregnancy, while in another, that of Schlesinger. it followed an abortion. Quite a number of cases hnally have developed after the menopause. Occasionally trauma is noted in the history, and the importance of this fact has been especially insisted upon by Guidiceandrea. In a case of the writer's and in one of Eshner's. trauma seemed to be the direct exciting cause. Emo- tional shock has also preceded the onset, as in the case of Achard and Laubry. In Vitaut's case there ap- peared to be a mild infection of the digestive tract ; in other cases expos- ure to cold and dampness, rheuma- tism, appeared to play a role. Occas- ionally also some other neurosis exists side by side with the affection, as in the woman reported by Henry and in a man reported by the w^riter. both of whom suffered from epilepsy. In other cases again, undoubted mental disease has been noted ; sometimes indeed, as in one of Eshner's cases, commitment to an institution becomes necessary. Case of adiposis dolorosa in a woman aged 80, the mother of 5 children, who had fallen 15 years be- fore, after which accident an opera- tion was performed upon her hip, some bloody fluid being evacuated. Since that time her legs have been weak. Pain appeared in the left hip and lumbar region, always along the nerves. She grew stouter very grad- ually. The fat is in large masses about the malleoli, hips, calves, but- tocks, abdomen, forearms, and backs of the arms especially. Debove (Presse med., July 17, 1901). Case in a woman, aged 61 years, who, with an apparently unimportant family history, dates her troubles from a fall from a chair years before. The left eye became blind, and the left side of the nose developed a tu- mor. The adiposis appeared in her thirtieth year, in the right leg first, and then in the left. The arms were next attacked. Pain accompanied all the early symptoms. When examined, the patient's neck and the subclavicu- lar region, as well as the abdomen, besides the limbs, were loaded with fat. An enormous fatty tumor was also i)resent on the internal aspect of the left thigh. The buttocks w^ere immense. The pores of the skin were enlarged. Pain, lasting two or three days, in the fatty region was not un- common. Sensation and temperature were normal; the corneal reflex was absent, as well as the patellar and Achilles. Mentality was normal, but there was great asthenia. The writers attribute the disease to some aflfec- tion of the pituitary. Delucq and Alaux (Presse med., Sept. 17, 1904). A typical case with the onset of the disease at the early age of 14, and the symptoms also unusual. Generally the deposits of fat are tender, and spontaneous pains (commonly of a neuralgic or rheumatic order) are slight and only appear occasionally; in this case, however, there was scarcely any pain on pressure, and there were spontaneous burning sen- sations and an inner sensation of great tension. The writer attributes ADIPOSIS DOLOROSA (DERCUM). 399 these intermittent pains to a probable accumulation of water in the fatty tissue, and perhaps in the muscula- ture also. Grafe (Miinch. med. Woch., Mar. 19, 1920). PATHOLOGY.— Up to the time of writing, eight autopsies have been held. These indicate that in adiposis dolorosa there is some disturbance of the internal secretions, excessive forma- tion of fatty tissue, and an interstitial neuritis of the nerve-fibers contained in the deposits. [Price has summarized, the results of the various autopsies as follows : — Cases I and II. — Dercum : Macroscopic disease of the thyroid, the glands being en- larged and the seat of calcareous infiltration. Case III. — Dercum: Irregular atrophy of the thyroid, extensive interstitial neuritis of peripheral nerves in fatty deposits, degenera- tion in the columns of Goll. Case IV. — Burr : Glioma of the pituitary body; colloid degeneration, with atrophy and absence of secreting cells in many acini of the thyroid gland ; interstitial neuritis of terminal filaments ; sclerotic ovaries. Case V. — Dercum and McCarthy : Adeno- carcinoma of pituitary body, thyroid nor- mal, right suprarenal gland hypertrophied, hemolymph-glands, interstitial neuritis, un- developed testicles. Case VI. — Guillain and Alquier : Hypoph- ysis doubled in size, with marked increase of connective tissue in the glandular portion and changes suggesting an alveolar carci- noma ; thyroid hypertrophied, with increase in connective-tissue stroma. Case VII. — Price: Inflammatory changes in thyroid, with marked increase in the inter- stitial connective tissue, one whole lobe being especially infiltrated, the other showing compensatory hypertrophy. Inflammatory changes in hypophysis, with presence of a condition suggesting alveolar or glandular carcinoma, interstitial and parenchymatous neuritis, sclerotic ovaries. Case VIII. — Price: Marked increase in _ the connective tissue of the thyroid gland, dilatation of the acini, with infoldings of the cuboidal epithelial lining. The same changes in the hypophysis as were found in Cases VI and VII, but less marked. No abnormalities of the adipose tissue. F. X. Dercum.] Delecq thinks that disease of the thyroid, testicle, ovary, and pituitary body may be causes of adiposis dolorosa. \"on Schroeter concludes that adiposis dolorosa is due to a dysthyroidismus. Pineles regards the disease as a result of the disturb- ance of function in numerotis blood- glands and that there are present hypothyroidism, genital atrophy, and changes in the hypophysis. The thyroid gland, it will be noted, showed unmistakable changes in 7 of the 8 autopsies. These changes are very interesting and are well illus- trated by the findings in the third autopsy of the writer, in which the gland was submitted to microscopic examination. A study of the sections reveals the gland to be made up of three or four different kinds of secret- ing tissue. In the first place, there are large acini distended by colloid material. These large acini vary in size, and their contents vary also in density. The larger acini are globu- lar in shape, while some of the smaller ones are elongated or angular in form. The limits of these acini are clearly indicated by blood-vessels which occupy their walls. The epi- thelium is a single layer, which covers uniformly the peripheries of the acini. Contrasted with these there is another kind of secreting tissue, which is very solid, and in which the acini are made out with great diffi- culty. They consist of cells filling interspaces of the stroma, and the blood-vessels supplying these acini can only be made out in exceptional instances. The lumina of these acini when they can be made out are usually very small. There is here a 400 ADIPOSIS DOLOROSA (DERCUM). complete absence of colloid material. In other portions acini are observed which are a transition between the more solid nests of cells and the larg'e vesicles which contain the colloid material. In addition, there is a third form of acinus, which is of peculiar interest in that the acini present plica- tions or papillary outs^rowths of the walls. These plications or out- growths project into the luinina of the affected acini, which contain, as a rule, colloid material of lighter staining qualities than the larger vesicles, although not lighter than is contained in some of the smaller vesicles. The epithelium of these last-mentioned acini ajipears at times to be slightly higher than the normal cubical epithelium of the other vesi- cles. Finally, in some areas, solid masses of cells resembling lymphoid cells are seen, l)ut these arc probably young solid acini, like the small acini described above, though the limits of these acini are irregular, because of the absence of preserved blood in the surrounding vessels and of the absence of definite interstitial frame- work. The changes observed are indica- tive in part of hypertrophy. Certainly this seems to be the only interpreta- tion which can be placed on the numerous small acini which appear to be in process of development. Whether the large acini, distended with more deeply staining colloid material, are to be considered old acini, containing old or altered colloid material, it is, of course, impossible to say, but such an interpretation does not seem improbable. The pli- cations and papillary outgrowths observed in some of the acini are also worthy of comment, in that they evidently represent an attempt to in- crease the secreting surface of the acini and are again expressive of hypertrophy. These findings are very surprising, and it is difficult, of course, to frame an explanation. It is not impossible that we have here a hypertrophy which is the direct outcome of a general atrophy of the gland ; in other words, a com- pensatory hypertrojihy such as Hal- stead obtained in the dog after partial extirpation. The ghuul was small, per- haps sufficiently so to determine com- pensatory hypertrophy. It is probable, however, that other factors, c.'^/ ■y Section of nerve in subcutaneous fat nodule showing interstitial neuritis. A distinct over- growth of connective tissue Is present between the nerve-fibers. The number of blood-vessels is also increased over normal nerve-tissue. (Der- •rum and McCarthy.) toms in adiposis dolorosa, we are justi- fied in accepting a kindred cause of both syndromes. That thyroid insuffi- ciency stands at the foundation of myxedema there can be little doubt ; again, some thyroid alteration was found in 4 out of 5 cases of adiposis dolorosa which came to autopsy. While the seat of the externally visible pa- thognomonic symptoms of myxedema is in the subcutaneous tissues, that of adiposis dolorosa is situated in the fatty structures. Moreover, the improvement of case reported following the administration of thyroid extract seems to evince with certainly that perverse thyroid function was, to say the least, an antecedent. The yielding of both symptom-com- plexes to the same medication again points to their interrelation or their springing from a kindred cause. Thy- roid therapy cannot, therefore, be util- ized as a test of differentiation between myxedema and adiposis dolorosa, as some authors maintain, because both syndromes may vanish under its in- fluence, and, i.s in the present instance, even at the same time. Ileinrich Stern (Amer. Jour. Med. Sci., March, 1910). Case of adiposis dolorosa in young soldier. The symmetrical and ex- treiuel}' painful subcutaneous lipomas were accompanied by profound as- thenia, with the picture of typical Dercum's disease. The first lipoma developed about 1 month after an exceptionally violent effort to lift a heavy stone, during vvhicli the shoulder had become dislocated. The pain was intense and the pre- viously rol ust young man grew weaker as more lipomas developed. They lay free in the subcutaneous adipose tissue and were easily re- moved. The writer concludes that the cause is some upset in the bal- ance of fat production, the result of multiple disturbance in the endocrine- sympathetic systems. C. Martelli (Tumori, May 18, 1918), The identity of Dercum's disease as a disorder of the sympathetic system was pointed out by Sajous in 1914. in a paper read before the Southeastern Branch of the Philadelphia County Medical Society, and also in abstract in the 1917 Supple- ment Volume of the Seventh Edition of the present work, page 65. Editors. DIAGNOSIS.— The diagnosis is based upon the presence of the fatty masses, presenting the feature of pain, spontaneous, paroxysmal, or elicited by manipulation, and having in addition the physical peculiarities ADIPOSIS DOLOROSA (DERCUM). 405 already described. The disease is readily differentiated from myxedema because of non-involvement of the face and hands and because of the absence of pain in myxedema. When the tumor masses are numerous and small, they might suggest neurofi- bromatosis, but the peculiar charac- ter of the swellings, the fact that they appear Icbulated under palpa- tion, that they are spontaneously painful and almost never occur upon the face or hands would serve to make the difTerentiation. In neurofibromatosis, again, there are two kinds of tumors, some of them cutaneous, not rarely on the face, and others on the mucous sur- faces. They are of soft, yielding con- sistence and very slightly painful. Others, those of nervous origin, are small, very hard, and often grouped along the course of the nerve trunks like a string of beads. They are only laterally mobile, while the adi- pose tumors are mobile in all direc- tions and are irregularly distributed. Again, anomalies of pigmentation are rare in adiposis dolorosa, but are frequent and sometimes very pro- nounced in neurofibromatosis. On the whole, it is hardly probable that an error could be made. In simple obesity, the fat is dis- tributed throughout all the tissues and does not heap itself up in separate lipomatous masses, such as is the case in adiposis dolorosa, — even in the so- called diffuse form. Besides, ordinary obesity is painless and is a matter of gradual development, while the fatty deposit in adiposis dolorosa is painful and occurs as the result of successive crises. PROGNOSIS.— Adiposis dolorosa is an affection which is essentially chronic. Most cases live for many years and it does not appear to imme- diately threaten life. However, in cases of long standing, a bed-ridden period eventually ensues; general exhaustion becomes more and more marked; degeneration and failure of the heart muscle, pulmonary conges- tion, or a renal complication may terminate the picture. The resistance to infection also appears to be greatly diminished, for one of the writer's cases died very rapidly of an attack of erysipelas. Cases in a relatively early stage of development — more particularly cases with small nodular or localized and limited deposits — offer a dis- tinctly better prognosis and are dis- tinctly amenable to improvement. Advanced cases, cases with very ex- tensive deposits, marked asthenia, and especially with tlie tendency to sub- cutaneous hemorrhages and hemor- rhages from the mucous membranes are very unpromising. TREATMENT.— In the treatment of adiposis dolorosa one remedy has in a few cases proved of value and that is thyroid substance. This should be given in doses of from 2j4 to 5 grains three times daily, for a very long time. The salicylates, notably aspirin, are of decided value in relieving the pain. The best plan of procedure, as a matter of course, is to place the patient in bed, and to institute a systematic course of treat- ment. The rest should be absolut^i and should extend over several months of time. Typical case with symptoms of myxe- dema in which the treatment consisted of an antiobcsity diet, thyroid medica- tion, and physical therapentics, especially vibratory massage and exercise. Nine months later the patient presented her- 406 ADIPOSIS DOLOROSA (DERCUM). self to show the beneficial effects of the treatment. Excepting the paUor, which, she said, had always caused her much annoyance since her early youth, she looked very well. She felt strong, and was able to walk from five to eight miles a day; she experienced no short- ness of breath on ordinary exercise, but perspired mildly when she walked briskly. The fat Linches had disap- peared almost entirely; the neuralgic pains had ceased about four months earlier; there was no tenderness on pressure on the location of the former fat masses. The skin in the supraclavic- ular regions and in the face had been quite tender. She evinced not the slightest mental depression and apathy, but, on the contrary, displayed a healthy optimism. Her weight had been re- duced to 161 pounds. Hcinrich Stern (Amer. Jour. Med. Sci., March. 1910). Case in a man of 32, married 6 months, which, the writer thinks, throws light on the etiology of the disease. The pressure of the man's body against his desk explained the unusual location of lipomas, and the immediate effect of an injection of pituitary extract on retention of urine confirmed the influence of the pituitary on the innervation of the bladder, but the primal factor in Dercum's disease seems to be some abnormal or lacking hormone from the organs of reproduction. This seems to upset the normal balance in the chromaffine system. His patient was clinically cured, even to the retrogression of the lipomas, bj' sys- tematic treatment with thyroid 1 part; pituitary, 1 part, and of ovary 2 parts, supplemented by a vegetable diet and exercise in the country. Whenever this treatment was inter- rupted, the whole set of symptoms returned, even including some of the tumors. The patient learned to make his organotherapeutic products him- self, making a cold extract of thyroid and testicles, 1:4, from sheep 1 or 2 years old. (Extraction cold; 50 c.c; phenol, 0.05.) He took a teaspoon- ful of this extract morning and even- ing in warm soup. The writer re- calls that Dercum in describing his first case of adiposis dolorosa noted its connection with the thyroid. Cecikas (Jour. Amer. Me4 grain (0.004 to 0.017 Gm.). It acts more promptly than digitalis. Inoko also obtained a glucosid — adonin — from the Japanese plant, Adonis amiirensis. This substance is free from nitrogen, amorphous, color- less, of a bitter taste, and soluble in water, alcohol, and chloroform. The effects observed on the heart of a frog were precisely those seen when digitalin is used. It is about twenty times weaker than the adonidin ob- tained from the European Adonis vernalis. PHYSIOLOGICAL ACTION.— Adonis resembles digitalis in its action upon the heart when given in therapeutic doses. It increases car- diac energy and raises the arterial tension. The increased contractions eventually diminish and a period of quiet follows, varying in duration with the dose administered. In frogs and dogs the watery ex- tract caused a marked slowing of the heart, owing to stimulation of the pneumogastric and its terminal branches, the blood-vessels being contracted and the blood-pressure raised. The alcoholic extract, on the other hand, had a very slight effect on the frequency of cardiac contrac- tions, but increased their strength and also dilated the blood-vessels, the blood-pressure remaining unafifected. SlovtzofT (Roussky Vratch, Sept. 15. 1912). The prevailing knowledge of the mode of action of adonis is based on experiments with the glucosid adoni- din. The results have, on the whole, been contradictory. While Cervello and Lesage found that it arrested the heart in systole, Iluchard and Hare ascertained repeatedly that this organ was arrested in diastole and Guirlet found the left ventricle in systole and the other cavities in diastole. There has been greater concordance in respect to its effects on the blood- pressure, all observers having found that there was first a rise, then a fall. While the primary slowing is at- tri])uted to the inhibitory action of the vagus, since its section prevented it, Hare found that the diastolic arrest was not due to this nerve, since it occurred after the latter was dixided, while galvanization of the nerve later on also failed to inhibit the heart. He concludes, therefore, that adonidin tends secondarily to paralyze the vagus — Kakowski, in fact, found that it caused dilatation of the coronaries instead of contrac- tion of these arteries. Hare's experi- ments indicate that it may also cause primary stimulation and secondary paralysis of the vasomotor system. Adonis has been credited with diuretic properties by Bubnow, Alt- mann, and Michaelis, though their observations have failed to be con- ADONIS VERNALIS (SAJOUS). 409 firmed by certain others. W'liatever diuretic power it may have is prob- ably the result of activation of the renal circulation (Wood). An unmistakable ciiinulative action and a maiked action on the heart was observed by the writer. The pa- tient had taken 6 Gm. (2^^ drams) of the drug^ in an infusion daily for 56 consecutive days — a total of 396 Gm. (ISVa ounces). He was a large man of 65, hearty, with mitral insufficiency and alcoholic cirrhosis. There were no signs that the drug was proving toxic, no headache, nausea nor pain in the stomach, but the pulse of 43 then developed a tj'pical bigeminus form. On suspension of the drug the beat returned to the normal type in I the course of 3 days. Mayor and Segond published in 1912 a research showing that the digestive juices have a destructive action on the active principle of adonis. Roch (Arch, des Mai. de Coeur, June, 1913). INCOMPATIBILITIES. — The glucosid adonidin in solution is de- composed by free acids or alkalies. It is incompatible with tannic acid, corrosive sublimate, and silver nitrate. The physiological incompatibilities of adonis include aconite, amyl nitrite, muscarin, veratrum viride. CONTRAINDICATIONS.— Ado- nis is contraindicated in arterioscle- rosis, in affections attended by a high vascular tension (as in the earlier stages of interstitial nephri- tis), and in hypertrophy and other disorders of the heart in which digi- talis, its physiological homologue, is harmful. THERAPEUTICS.— Adonis is use- ful in cases of valvular heart disease with loss of compensation and in which evidences of grave circulatory disorder, such as cardiac asthma, are present. It has been specifically recommended in aortic and mitral regurgitation. The diuretic powers of the drug cause it to be of value in cases of dropsy and cardiac degeneration. It is also valuable in palpitation dependent upon irregular inhibition. As it does not seem to possess cumulative tend- encies, it may be administered with more freedom than digitalis. Accord- ing to Dujardin-Beaumetz, however, large doses cause gastric disorders and vomiting. Borgiotti found adonis valuable in different cardiac disorders. One dram to 1 ounce of the infusion daily constitutes an excellent cardiac tonic. In fatty degeneration of the heart it increases diuresis and regulates the circulation. Adonidin is credited with proper- ties superior to digitalis, in that it acts more promptly and with less tendency to cumulation. As Dujar- din-Beaumetz had observed in the case of the infusion of adonis, how- ever, Lublinski and Durand have found adonidin to produce violent gastrointestinal disorders Avith diar- rhea and vomiting. According to Dujardin-Beaumetz, the dose should never exceed % grain (0.02 Gm.) ; lluchard gives Vi2 gi'ain (0.005 Gm.) three or four times daily in adults. As a remedy for the reduction of obesity, adonis aestivalis has proved of value. Owing to the fact that it does not possess a tendency to cumu- lation, it may be continued for a long time. It is claimed to have been effective in relieving the heart from an excessive covering of fatty tissue. The tincture of this species may be given in doses of 10 minims (0.6 c.c.) three times daily. To reduce the active cerebral hyperemia present during a paroxysm of epilepsy adonis has been recom- mended, owing to its power of stimu- 410 ADRENALS, DISEASES OF (SAJOUS). lating the vasoconstrictors. It may be advantageously combined with the bromides. C. E. DE M. Sajous AND L. T. DE M. Satous. Philadelphia. ADRENALIN.— See Animal Ex- tracts: Adrenals. ADRENALS, DISEASES OF THE.— Although it is the purpose of this Cyclopedia to present the prevail- ing or current views upon the subjects treated, the writer does not feel that he can conscientiously observe this rule in the present instance. Having probably devoted more time to the study of the ductless glands and to a comparative analysis of the work done l)y others than any other investigator in this comprehensive field, he does not hesitate to state that the physio- logical roles that physiologists now attribute to the adrenals are not true functions but merely secondary ex- pressions of a function hrst described by myself in V)05. It is, briefly, that the adrenals sustain tissue oxidation and metabolism by contributing an oxidizing ferment to the hemoglobin. What I deem to be only manifesta- tions of that function, are : (1) ()li\er and Schafer's theory that the adrenals sustain the cardio-vascular tone ; (2) Cannon and La l^az's emergency theory, in which the adrenals are thought to secrete only under the stress of ex- citement, fear, anger, etc.. and (3) Abelous and Langlois' theory in which the adrenals are thought to carry on an antitoxic role, mainly for the de- struction of fatigue wastes. All these theories have been severely attacked by other physiologists, Stewart, Hookins, Gley and others, and it is generally considered at present that they are obsolete. From my view- point, however, such is not the case, for if, as I hold, the adrenals govern respiration and tissue oxidation (a function admittedly obscure accord- ing to physiologists), it is but normal that they should sustain the vascular tone, secrete abnormally under the influence of excitement, and take part in ])reaking down fatigue wastes. It has also been shown that adre- nalin is able in small doses to lower the blood-pressure. This is due from my vie\vi)oint to the fact that it ■primarily causes constriction of the vasa vasorum ; the arterial supply of the vascular muscularis being re- duced, the vessels dilate. To understand the role of the ad- renals in disease it is important to understand the following: — The Adrenal Secretion in Pulmonary and Tissue Oxidation. — The prevailing dif- fusion doctrine as to the absorption of oxygen from the pulmonary air and the elimination of carbonic acid, having been shown by Paul Bert, Miillcr, Setschenow and Holmgren, Bohr and other authorities to be defective, Bohr concluded in 1891 that some internal secretion capable of tak- ing up the oxygen from the air in the lungs was necessary to explain the process. A comprehensive study of the question led me to the conclusion that it was the internal secretion of the adrenals which carried on this all important function. The following are but a few of the main factors in support of this opinion: 1. The marked affinity of the adrenal secre- tion for oxygen, sustained by the experi- mental observations of Vulpian, Cybulski, Langlois, Battelli, Abel, Takamine and others, including the writer. 2. The presence of the adrenal secretion in the venous blood between the adrenals and the pulmonary air cells, sustained by the experimental observations of Gottschau, Alanasse, Aulde, Stilling, Pfaundler, Cybul- ski and Scymonowicz, Biedl, Langlois, Dreyer, ADRENALS, DISEASES OF (SAJOUS). 411 Salvioli and Pizzolini and personal ana- tomical researches. 3. The marked reducing power of the blood coursing in the zvalls of the air-cells, shown by the experiments of Ivobin, Verdeil, Garnier. and Miiller. 4. The presence in the hemoglobin, of a constituent whose physicochemical properties are those of the adrenal secretion, sustained by the observations, first, of Vulpian, Gaut- ier. Moore, Moore and Purinton. and Cybul- ski as to the properties c f the adrenal prin- ciple ; those of Battelli, Dixon and Young as to the presence of the adrenal principle in the blood ; of Mulon as to its presence in the red corpuscles: of Schmiedeberg. Jaquet, Abelous and Biarnes, and Salkowski, and my own as to the presence of an oxidizing fer- ment in the blood ; of Jolles and Poehl as to the catalytic and oxidizing properties of the adrenal components of the blood. 5. The adrenalin secretion can endow hemoglobin with its oxygen-carrying poiver sustained by the observations of Menten and Crile (1915) that the blood of the adrenal vein invariably assumed a bright red color in from one to twenty minutes after dilution with salt solution, while blood from other organs tieated in the same manner showed no change — a tact found spectroscopically to be due to an increased formation of oxyhemoglobin. Again. Menten (1917) having added ad- renalin to diluted human venous blood, found that it caused an increase in the in- tensity of the oxyhemoglobin absorption bands. 6. The presence of the hemoglobin con- taining the adrenal principle in all parts of the body, including the skin, sustained by the presence of melanins everywhere and their identity as hemoglobin derivative and as the adrenal principle based on the investigations of Leonard Hill, Hirschfeld, Chittenden and Albro as to melanin being an hemoglobin derivative ; those of Boinet, Miihlmann, and myself as to the identity of melanin (the bronze pigment of Addison's disease) as a product of the adrenals. 7. The marked influence of the adrenal secretion and preparations upon the tem- perature, general oxidation, and metaholisni, sustained by the observations of Reichert, Morel, Lepine, Israel, and others, including myself, as to their ability to cause a rise of temperature; those of Brown-Sequard and many others, as to the steady decline of tem- perature following removal of the adrenals, or occlusion of the adrenal veins ; the hypo- thermia of Addison's disease ; the observa- tions of Byelaventy, loteyko, Dessy and Grandis, and others, includi..g myself, as to the increased gaseous interchanges and cellu- lar metabolism, and the increase in the elimination of waste products caused by the adrenal principle. The Adrenal Secretion in Immunity. — The adrenal secretion in this connection is, from my viewpoint, but ow^ of the antibodies which carry on this process, being what has been termed by Bordet the "fixative'' or "specific immunizing body" and by Ehrlich "amboceptor." Referring to "Internal Se- cretions" for details which cannot be em- bodied here, upon this phase of the question, I will limit myself to the direct relationship of the adrenals with the autoprotective functions : — The adrenals are knotvn to carry on anti- toxic functions. Sustained by the observa- tions of Albanese (1872), which showed that removal of the adrenals reduced the resist- ance to poisoning by neurine ; those of Abel- ous and Langlois (1892-1898), which showed that the adrenals neutralized poisonous sub- stances derived from muscular activity and bacterial products, and also by the investiga- tions of Mosse. Additional testimony is afforded by the marked evidences of over- activity shown by the adrenals under the influence of certain waste products and tox- ins, as noted by Langlois and Charrin, Petit, Stilling, Auld, Wybaux, and others, and also by the protection afforded by adrenalin in- jections against strychnine injections ob- served by Oppenheim, Meltzer and .\uer and various toxemias and infections as observed by Hoddick, Netter, Marran and Dare, Moizard, Kirchheimer, and many other clinicians. The relationship between the adrenals and general oxidation, shown above, also estab- lishes a connection with the production of fever, which, in the light of modern work is also considered, up to a certain limit, as a defensive process. C. E. de M. S.] To disregard functions of such im- portance would make it impossible to account for many phenomena awak- 412 ADRENALS, DISEASES OF (SAJOUS). ened by disorders of the adrenals, and correspondingly limit our usefulness in the practical field. This entails, how- ever, the necessity of granting to the adrenals a position in pathology equal to any of the major organs. Indeed, the functions I have attributed to them, in addition to those with which they are already credited, entitle them to rank pathogenically with the heart and blood- vessels in so far as the general vascular pressure is concerned, and the lungs in respect to respiration and tissue oxida- tion. When, moreover, their role in the autodefensive or immunizing proc- esses of the body is also taken into ac- count, their importance may almost be said to exceed that of other organs; since they thus not only serve to sustain life through tissue oxidation, but also to protect life through their role in im- munity. CLASSIFICATION.— Impairment of these functions to any extent, through factors which either inhibit or exaggerate the secretory activity of the adrenals, must necessarily awaken symptoms which indicate the functional disorders present. In Addison's disease (treated by Prof. T-anglois. of Paris. earlier in the present volume), for example, where destruction of the ad- renals or of their secretory nerves by a local lesion correspondingly compro- mises their fvmctions, wc have as main phenomena not only the vascular hypo- tension and cardiac weakness which the well-known action of the adrenal secre- tion on the blood-pressure explains, but also the low temperature, the general coldness, the dyspnea and the gradual emaciation which deficient oxidation alone accounts for. Now if. from any cause, the functions of the adrenals are inhibited, we have a reproduction, more or less marked according to the degree of inhibition, of these morbid phenom- ena. They form the symptom-complex of the condition best designated by the term "hypoadrenia." [This term was selected owing to its greater exactness and brevity than "hypoad- rcnalism," and owing to the fact that the latter suggests the presence of a habit such as "alcohohsm." It is obviously less cum- bersome than "insufficiency of the adrenals" or "adrenal insufficiency," and corresponds with terms in current use such as "anemia," "asthenia," etc. In 1899 Sergent and Bernard (Archives Generales dc Medecine, July) were the first to advance the view that adrenal insufficiency was a syndrome due to destruction of the adrenals, but standing apart from Addison's disease, which they ascribed mainly to lesions of the abdominal sympathetic. My own re- searches ("Internal Secretions," vol. i, 1903. and ii, 1907) sustained the opinion of many other observers, however, to the effect that the elimination of Addison's disease was not warranted, and that this disease presented the most comprehensive external picture of grad- ual destruction of the adrenals or of the periadrenal sympathetic structures, or of these structures and the adrenals jointly, i.e., of adrenal insufficiency. Again, Sergent and Bernard ascribe the syndrome of adrenal insufficiency as a whole to a general intoxication which they divide into fulminant (sudden c'cath), acute (rapid autointoxication), and subacute (slow auto- intoxication). From my viewpoint, however, all the symptoms excepting the convulsions are due to the inhibition of functions which are primarily dependent upon the adrenals : viz., general oxygenation, metabolism, and nutrition. The only intoxication phenomena, the convulsions witnessed in these cases, I ascribe to the accumulation of toxic wastes (shown by Abelous and Langlois to be an- tagonized by the adrenal secretion) which are not broken down with sufficient rapidity when the oxidation processes sustained by the adrenals are inhibited. C. E. de M. S.] Of the various forms of hypoadrenia is one which is practically unrecognized, though frequently a cause of death, mainly among children, viz. : — ADRENALS, DISEASES OF (SAJOUS). 413 TERMINAL HYPOADRENIA. DEFINITION.— Terminal hypoad- renia is a form of marked asthenia which occurs late in the course of an acute febrile disease as a result of ex- hausting secretory activity of the ad- renals— acting as defensive organs — in the course of that disease. [The term "terminal" is ' serted here be- cause it is important to differentiate this form of hypoadrenia from that which occurs early in the course of a toxemia and known as adrenal hemorrhage, treated farther on in this article. C. E. deM. S.] PATHOGENESIS AND SYMP- TOMATOLOGY.—The adrenals be- ing admittedly concerned in the protec- tion of the organism during infections and intoxications, by contributing an excess of their secretion during the febrile stage of the disease (sometimes considerably prolonged), it follows that, after this stage is over, the adrenals should lapse into a condition of more or less temporary insufficiency through fatigue or exhaustion. That other or- gans concerned in the immunizing pro- cess are influenced in the same way must doubtless be the case, but the fact remains that it is the symptomatology of hypoadrenia that is uppermost. In lobar pneumonia and broncho- pneumonia, for instance, resolution may be considerably delayed and convales- cence likewise. There is. late in the case, extreme advnamia and a low blood-pressure, the temperature is below normal, the pulse weak and more or less rapid, and death from heart-failure is not infrequent. In typhoid fever, hypo- adrenia is commonly observed. The disease assumes what is now known as the cardiac type, with, late in the case, extreme prostration, a rapid, weak and sometimes irregular pulse, hypothermia, and a marked tendency to vertigo, faint- ing, and cardiac failure. [Sicard (Bull, de la soc. med., July 21, 1904) reported the case of a young woman in whom the foregoing symptoms appeared on the ninth day of a bronchopneumonia. Extreme muscular weakness, marked hypo- thermia and low blood-pressure, diarrhea, and Sergent's white line, which denotes marked adrenal insufficiency, were present. On the fifteenth day the blood-pressure fell to 70 or 80 (7 or 8 per cent, potain) and death followed three days later. At the autopsy the adrenals were found hemor- rhagic. This suggests that adrenal lesions may be present in all such cases. Yet, Ribadeau-Dunias and Bing (Bull, de la soc. anat., June 3, 1904) have witnessed the same symptoms in cases of measles which recovered, while Bossuet (Gaz. hebd. des sci. med. de Bordeaux, Oct. 30, 1904) refers to 8 cases in various febrile disorders in which typical symptoms of adrenal insuffi- ciency, asthenia, low blood-pressure, etc.. developed suddenly and disappeared spon- taneously, aided perhaps by adrenal extract which had been administered. As stated recently by Morichau-Beauchant (Le progres medical, Oct. 9, 1909), the ad- renals seem to show a special predilection for certain infections. Diphtheria easily leads them all in this connection. So seri- ously do these organs suffer in these cases that Sevestre and Marfan have termed the type "secondary syndrome of malignant diphtheria." Hutinel ascribes the fulminat- ing cases of scarlatina to this cause. Tet- anus, erysipelas, mumps, certain forms of tonsillitis, and certain streptococcic infec- tions may also present the typical syndrome of hypoadrenia. Goldzicher (Wiener klin. W'och., June 10, 1910) was led by his re- searches to conclude that in the various forms of septicemia the appearance of lower blood-pressure was to be ascribed to in- sufficiency of the adrenals. C. E. de M. S.] When, at the end of an infectious disease, the case, instead of proceeding to convalescence, remains in a condition of asthenia, with low blood-pressure and temperature, there is good ground for the conclusion that terminal hypo- adrenia has occurred. Exhaustion of the adrenals during the acute process having inhibited the secretory activity 414 ADRENALS, DISEASES OF (SAJOUS). of these organs, the above symptoms result from inadequate oxidation of, and metabolic activity in, the tissues. Sergent's white line, brought about by gently rubbing a narrow streak over any part of the abdomen with the finger, may be obtained in the majority of these cases. After a short period the area becomes whitisli and remains so a short time. The writers found the white line present in 145 out of 228 cases; 65 of these had hypotension and 80 a nor- mal or hypertension. The 83 cases which did not give the test included 30 with hypotension and 53 with nor- mal or hypertension. The 80 cases with the white line without hypoten- sion and 3U with hypotension with- out the white line make a total of 110, or one-half of the 228 cases tested, which do not conform to the. rule. They conclude that the white line cannot, therefore, constitute a sign of either adrenal insufficiency or hypotension. Lautier and Gregoire (Soc. de biol., vol. Ixvii, p. 690. 1910), In a special research for the pres- ence or absence of Sergent's white line in 100 sick or wounded soldiers in a garrison infirmary, the line was elicited in 81. It was present in all but 2 febrile cases and in 17 out of 20 subjects with gonorrhea. It was never absent in grip, rheumatism, malaria, or tuberculosis, and was en- countered in a variety of purely local conditions, as gingivitis and orchitis. The writer concludes that the white line is of great value in certain emer- gencies of differential diagnosis, as when acute adrenal insufficiency is con- fused with a pyrexia of meningeal, thoracic, or abdominal origin. Its association with certain infections like grip and rheumatism means a certain degree of asthenia and hypo- tension, and betrays the implication of the adrenals in the disease picture, though not as serious as acute ad- renal instifficiency, with collapse, and does not carry a bad prognosis. Finally, when encountered in associa- tion with some trivial local condition, it represents a mere coincidence, or is due to a transitory disturbance of vasomotor equilibrium. Baudron (Jour, de med. et de chir. prat., July 25, 1918). The patient complains of chilliness ; the surface is pale, owing to the poverty of the blood in cellular elements and hemoglobin, and to recession of the blood-mass from the surface to the deeper vascular trunks. The vascular tension being low, the pulse is rapid and the heart-beat weak. Anorexia, due to deficient metabolism and diminished de- mand for food, nausea, the result of re- laxation of the gastric muscular coat, and diarrhea, due to a similar condition of the muscular coat of the already pas- sively engorged intestine, and more or less frequent fainting si)ells, are all con- comitant symptoms that may be wit- nessed in such cases, which are always greatly exposed to relap.se or to sudden death from heart-failure. The author has observed nine cases of acute suprarenal insufficiency of variable intensity, ending in recovery. The symptoms develop very rapidly, and, besides, they can disappear spon- taneously, at the same time with the illness which they accompany, for this acute adrenal insufficiency is due to an infection or an intoxication. The writer has always noted that the insufficiency occurs in the course of a toxic or infec- tious malady, medical or surgical. G. Bossuet (Gaz. hebd. des Sci. Med. de Bordeaux, Oct. 30, 1904). Case of acute insufficiency of the adrenals in an apparently healthy farmer who had been doing some hard work, exposed to the sun for several hours, when suddenly he col- lapsed with intense abdominal pain and headache, with great prostration. On the presumptive diagnosis of sun- stroke, he was treated with cold to the head and purgatives, but the symptoms persisted, soon accompa- nied by vomiting and hiccough; the ADRENALS, DISEASES OF (SAJOUS). 415 prostration increased, with a ten- dency to stupor; there were intense headache and delirium, respiration was superficial, the pupils were di- lated and did not react to stimuli, the heart-sounds became faint and death occurred at the end of the week. The only pathological findings at autopsy were atrophy of the adrenals from a sclerotic process in the veins, and compression from a hematoma from rupture of one of the veins in the adipose tissue surrounding the left suprarenal capsule. The writer at- tributes the acute insufficiency in his case to excessive exposure to the heat of the sun. Sotti (Policlinico, Jan. XV, Med. Sec. No. 1, 1908). Symptoms arising in the course of scarlatina which are very suggestive of insufficiency of the suprarenals. The symptoms are asthenia, depres- sion, failure of the heart-power, hypo- tension of the arteries, tendency to syncope, abdominal pains, and a brown coloration of the skin. The use of small doses of adrenalin had a remarkable effect in the cases cited, the patient recovering after being in an apparently desperate condition. V. Hutinel (Le bull, med.; Med. Record, Sept. 18, 1909). The 2 most prominent symptoms of terminal hypoadrenia in typhoid fever, acute nephritis, piieuiiioiiin, scarlet fever, and diphtheria, noted by the writers, were a sudden fall of blood-pressure and extreme prostra- tion but hypothermia, vomiting, a profuse green diarrhea, and an ery- thematous rash were also commonly observed. The adrenal lesions were found to differ, being either hemor- rhagic, or granulofatty, and ending in necrosis. Dumas and Hervier (Bull. et mem. de la Societe med. des Hop. de Paris, 1913). The symptomatology of the term- inal hypoadrenia in the various in- fections, measles, diphtheria, erysipelas, scarlet fever and others, is virtually identical in all, asthenia, low blood- pressure, prostration, hypothermia, vomiting, pain in the epigastrium, though two or more of these symp- toms may dominate the picture. Daily doses of 12 to 20 minims of adrenalin daily in such cases, cause the disease to lose its menacing char- acter as regards cardiac arrest. V. Hutinel (Arch, de Med. des Enfants, March, 1915). The writers observed 3 cases of sudden death from pernicious malarial fever in soldiers. In all 3 cases there was hypotension coinciding with maintenance of regular cardiac rhythm. In 1 of the cases the supra- renal white line pointed out by Ser- gent was clearly identified. In all 3 cases there were found lesions of the adrenal cortex. Paisseau and Le- maire (Acad, de Med., Oct. 17, 1916; Monde Med., Jan., 1917). The adrenals are frequently in- volved in camp diseases, including dysentery, malaria and gas gangrene. and the writer reports a case of anthrax septicemia in which cardio- vascular disturbances were pro- nounced from the first. The young man suffered from intense pain in the epigastrium, with profuse vomiting and final hematemesis, evidently due to eliinination of the microbes or their toxins by the gastro-intestinal mucosa. The extremely low blood- pressure and imperceptible pulse were explained by the necropsy find- ings of edema of the anterior medias- tinum, compressing the pericardium, and destruction of the left supra- renal by a recent hemorrhage. Roger (Paris med., July 14, 1917). Complications of various kinds may occur. The immunizing processes be- ing greatly weakened through the defi- ciency of adrenal secretion, one of its important factors, septic infection, ab- scesses, bone lesions, tuberculosis of a rapid type, and other infections may more or less rapidly develop. Disorders of nutrition, cholelithiasis, and occa- sionally Addison's disease may also appear. In acute pulmonary infections, pneumonia, for example, organs in the neighborhood of the focus of infectiorif 416 ADRENALS, DISEASES OF (SAJOUS). the pleura, the mediastinal glands, etc., being inadequately protected by the blood or its phagocytic cells, become the prey of specific bacteria. Briefly, the body is rendered vulnerable to the attacks of almost any pathogenic organism. PATHOLOGY.— In the special type in question no adrenal lesion may be discernible. In the majority of in- stances, however, the organs are en- larged and congested and may show, here and there, a limited hemorrhagic area. Their appearance suggests not only the functional torpor incident upon functional exhaustion, but the presence of a passh'c congestion resulting from loss of resiliency of their sinusoidal ves- sels, thus impeding the circulation through them. Occasionally they are t!ie seat of suppuration, a complica- tion which is ai)t to be observed when the causative disease is, or includes, a streptococcic infection, pneumonia, or meningitis. The pathological picture of the more severe form of adrenal complications, i.e., intercurrent hypcradrcnia, shows far more distinct lesions of the adrenal parenchyma. Hence the typical lethal phenomena that attend many of these cases. Mott and Halliburton have found already that in cases of death from exhausting diseases the adrenalin present in the adrenals was dimin- ished or absent. The writers have extended these observations; they have examined the adrenals in the cases of 50 adults dying from various diseases. The glands were placed in Cohn's fluid for twenty-four hours and afterward stained with Schar- lach or Sudan III; by this method the chromaffinic substance and the fat were demonstrated. They relied upon this demonstration of the amount of chromaffinic granules in the cells of the medulla, and did not carry out the physiological test. No appreciable loss of the substance oc- curred during twenty-four hours fol- lowing death, as told by control ex- periments in animals. Adrenalin was always being given off, especially if the splanchnics were stimulated. The conclusions drawn from their work were that in cases of acute infection and rapid death adrenalin was absent in the medulla; this applied also to cases of death from shock and from peritonitis when, in short, the blood- pressure was low. On the contrary, in chronic diseases, such as phthisis, adrenalin was to be found in the me- dulla. In cases of high blood-pres- sure adrenalin was present and dis- tinctly increased. F. A. Bainbridge and P. R. Parkinson (Brit. Med. Jour., Mar. 11, 1907). In 25 experiments on guinea-pigs and hedgehogs, the writer found that in only three was the microscopic condi- tion of the adrenals approximately nor- mal, while in the remaining 22 very characteristic changes were present, which in 18 were of serious degree, con- sisting of hemorrhages and necroses, alone or combined, after poisoning with the diphtheria toxin. Strubell (Berl. klin. Woch., March 21, 1910). The influence of di/^htlieria toxins upon the secretory activity of the ad- renals is well shown by personal ex- periments in which poisoning of an animal with diphtheria toxin was found to cause, at first, an increased proportion of adrenalin in the blood and subsequently a gradual decrease until total disappearance of the ad- renal principle had occurred. Tsche- boksarofif (Berl. klin. Woch., June, 1911). The writer convinced him that these organs are invariably the seat of lesions, and that the gravity of the latter depends more upon the inten- sity of the attack than upon its dura- tion or associated infections. Molts- chanow (Rev. del Circ. Med. Argen- tino, Nov.-Dec, 1912). The writers found that acute peri- tonitis showed a very marked reduc- tion of adrenalin, and that in 50 per ADRENALS, DISEASES OF (SAJOUS). 417 cent, of the cases of this disease examined post mortem, the adrenal cortex showed marked histological lesions. The authors conclude that acute peritonitis takes the lead among infections in the production of ad- renal lesions, a fact which explains the circulatory failure so marked in this disease. Reich and Beresnogow- ski (Beitr. zur klin. Chirurgie, May, 1914). TREATMENT.— In these particu- lar ca.se.s the use of adrenal gland, or of pituitary body, which acts very simi- larly l)ut with less violence and more lasting effects, sometimes gives surpris- ing results. The adrenal product — which, from my viewpoint, is also the main active agent in the neural lobe of the pituitary, as shown- by the chromaf- fin test — supplies precisely what the body needs, e.g., the resumption of all oxidation processes (thus restoring gen- eral metabolism and nutrition), and a rise of blood-pressure, which causes the blood to circulate normally in all organs, including the skin and the adrenals themselves. Indirect effects are also obtained: its action on the heart in- creases the contractile power of this organ, which is thus rendered capable of projecting the blood with more vigor through the lungs, and causes oxygena- tion of the blood to become more per- fect. Recovery is also materially aided by the rise of blood-pressure that the adrenal product insures, causing, as it does, arterial blood to be driven from the splanchnic area toward the periph- eral organs, including the lungs and the brain. From these features alone considerable benefit is derived. If we recall, moreover, the participa- tion of the adrenal secretion (which the adrenal preparation administered repre- sents) in the immunizing process, we have the added factors of ridding the blood of any intermediate — and there- 1—27 fore toxic— wastes, bacterial toxins, etc., it may contain, and of increasing phagocytic activity, thus antagonizing efiiciently any pathogenic organism that may remain to compromise the issue. Thus explained, we can understand the phrase, "little short of marvelous," applied to the results obtained by some clinicians. \Yt can also understand the marked reduction in the mortality ob- tained by Hoddick (Zentralbl. f. Chir., Oct. 12, 1907) in cases of peritonitis following appendicitis accompanied by uncontrollable decline of the blood- pressure, cyanosis, and other evidences of collapse, and also in puerperal toxe- mias, by the slow intravenous use of ad- renalin in saline solution. Hoddick as- cribes the lowering of the blood-press- ure to paralysis of the vasomotor cen- ter; but as the toxemia is the cause of this condition, an agent capable of coun- teracting both cause and effect is neces- sary. This is met by the adrenal prin- ciple. Josue (Soc. Med. des Hopitaux, May 21, 1909), in typhoid fever, like- wise relieved threatening symptoms by injecting 15 minims (1 c.c.) of adrena- lin (1:1000 sol.) in ](. to 1 pint (250 to 500 c.c.) of physiological saline solu- tion subcutaneously. The influence of the saline solution in these cases must not be overlooked, however. Eight years ago I urged that death was often due, in infectious and septic diseases, to the fact that the osmotic properties of the blood became deficient, and advised the use of saline solution from the onset of the di,sease. The reduction in "the mortality of pneumonia in the practice of men who have carried out this sug- gestion has demonstrated its value. [Several clinicians have employed much larger doses of the adrenal active prin- ciple with profit. Marran and Darre (Jour, des praticiens. May IS, 1909) found it of great value in the collapse of diphtheria 418 ADRENALS, DISEASES OF (SAJOUS). with marked asthenia, low blood-pressure, and subnormal temperature. Moizard (Re- vue de therap., Jan. 1, 1910) recommends ad- renal organotherapy as soon as asthenia and low blood-pressure occur in any infection. He gives daily two sheep's fresh adrenals, finely divided and mixed with powdered sugar, or administers the active principle, 10 to 20 drops daily divided in five or six doses. Kirchheimer CMiinch. med. Woch., Dec. 20, 1910) has found large doses, 10 to 24 min- ims, safe hypodermically in the collapse of pneumonia, diphtheria, and scarlet fever. Letulle has found it of great value in the latter disease. The better plan, from my viewpoint, is to inject it with saline solution (at 108° F.), intravenously, the needle of the syringe containing the adrenalin being in- serted into the rubber tube of the saline solution apparatus. C. E. de M. S.] If adrenal insufficiency arises during the progress of diphtheria, the writer advises combining suprarenal opother- apy with serotherapy. If syphilis is also present, suprarenal opotherapy may be associated with mercurial treatment. In the other infectious diseases, where no specific medication exists, opotherapy should be begun from the beginning of the symptoms of suprarenal insuffi- ciency. Adrenalin may be given by the mouth, or, if the hypodermic method is used, 1 c.c. of a 1 : KXX) solution is added to 50 grams of normal salt solu- tion and injected into the subcutaneous tissue. .\s this medication is inoffen- sive, it can be continued daily until the accidents of suprarenal insufficiency have disappeared. Comby (Archives de med. des enfants, Jan., 1911). To ascertain the most efficient dosage of adrenalin to counteract cardiovascular failure in pneumonia, typhoid and paratyphoid fever, the writer compared the effects of vari- ous doses in 30 patients. She found that 0.5 c.c. (8 minims) of adrenalin caused a moderate rise of blood-pres- sure which could be sustained by re- peating the dose hypodermically every hour or hour and a half. This dose was found to be the most effi- cient for infectious diseases. Mans- vetova (Roussky Vratch, July 4, 1914). The writer calls attention to the morbid effects of the hardships of the European War as causes of hy- poadrenia. through traumatic shock, major injuries, typhoid fever, typhus, cholereiform diarrhea, Asiatic chol- era, chloroform anesthesia, exhaus- tion, etc. Such cases are not met by 10 to 15 drops of adrenalin 1:1000 solution. He gives Vso to Via grain (2 to 3 milligrams) divided into 4 to 6 doses hypodermically, and in addi- tion \{\{) to ^fio grain (1 to 2 milli- grams) orally. He is convinced of having successfully combated col- lapse with such doses which other- wise would have ended iatally. Ser- gent ( lUilletin de I'Acad. de Med., Sept. 7. 1915). In the hypoadrenia of pneumonia, diphtheria, and typhoid fever, the writer found a combination of pituitrin and adrenalin, 0.25 c.c. (4 minims) oi the former, and 0.5 c.c. (8 minims) of the latter, intraven- ously in young children and twice these doses in older children restored failing circulation more actively than all other agents. This confirmed the results of Kepinow, who had pre- viously urged this combination. Roh- mer (Miinch. med. Woch., June 16, 1914). The essential symptomatic triad of adrenal insufficiency in asthenia, is low blood-pressure, and Sergent's white line. In some cases adrenal insuffi- ciency constitutes the entire clinical picture and seems primary; yet often close examination reveals a causative infection, at times very slight, e.g., a mild throat inflammation or intes- tinal infection. Other forms com- prise the adrenal overstrain of soldiers; the adrenal insufficiency of infections, such as typhoid, diphtheria, and tuber- culosis; that due to alimentary or other forms of into.vication; that of cardiac dilatation. The solar syndrome (skin discoloration and lumbar pains), the latter due to involvement of the peri- capsular nerve ganglia, may also be present. In such cases, extracts of the total gland sometimes prove dis- tinctly superior to the pure adrenalin ADRENALS, DISEASES OF (SAJOUS). 419 otherwise used. Both these products, repeatedly given, exert a regenerat- ing action on the adrenals. Their hypodermic and oral administration is free from the danger of causing arterial atheroma. Adrenalin by mouth gives good results provided it is used in sufficient amounts — 1 to 4 and even 5 c.c. (16 minims to 1 or 1^4 drams) of the 1: 1000 solution a day, divided into two intervals. Three c.c. (48 minims) may be thus given daily for a month or more without harm. For hypodermic use the dose is 0.5 to 2 c.c. (8 to 32 minims) a day, 0.5 c.c. being preferably not exceeded as the single dose. Such injections are generally more or less painful. Slow absorption of adrenalin is secured by injecting under the skin 250 to 500 c.c. (^2 to 1 pint) of normal saline solution to which 1 c.c. (16 minims) of adrenalin solution has just been added. The skin is. usually blanched at the point of injection and the ad- renalin is only with extreme slowness absorbed through the contracted ves- sels. The pain attending this pro- cedure is prevented by adding 0.01 Gm. (Vti grain) of novocaine to the solution. The injections may be con- tinued for se\ eral days. Extracts of the whole adrenal may be given orally in daih' amounts of 0.2 to 0.4 Grn. (3 to 6 grains), divided into 0.1- to 0.2- Gm. (1K> to 3 grains) doses, or hypodermicallj' in a daily amount of 0.1 Gm. (1^2 grains). Josue (Paris med., Jan. 6, 1917). Adrenal insufficiency is a rather frequent complication of amebic dj'sentery, m.anifested in marked gen- eral depression, asthenia, a feeble pulse, etc. In the case of a soldier on the Franco-Belgian front, stationed where Senegalese and Moroccan troops had recently been, the onset of diarrhea was accompanied !)>• prostration and tachycardia. Careful examination revealed no organic dis- turbance save in the liver, which was slightly tender and distinctly en- larged. The number of stools rose as high as 45 in 24 liours. The white line phenomenon was elicited on the abdomen and the pulse remained thready at 120 a minute. The dias- tolic blood-pressure descended to 70 mm. Hg. (Pachon instrument). Eme- tine hydrochloride in divided doses, to the total amount of 0.06 up to 0.1 Gm. (1 to iy2 grains) per diem, to- gether with adrenaline and camphor- ated oil, within a few days placed the patient on the road to recovery. The use of adrenaline is especiallj' recom- mended where there are signs, even slight, of impairment of the adrenals due to toxic action of the amebse on these organs. R. Dujarric de la Riviere and Villerval (Paris med., Apr. 21, 1917). Case in which there was unusually marked pigmentation, disappearance of the pigmentation followed supra- renal treatment. The loss of mus- cular strength, due to suprarenal de- ficiency, was very inarked. Osborne (Amer. Jour. Med. Sci., Aug., 1918). These measures are only indicated in emergency cases, however. In the average case the glandulae suprarenales siccae of the United States Pharmaco- peia, administered by the mouth, is fidly as effective if a good preparation is obtained as soon as asthenia and low blood-pressure appear. The powder in 3-grain (0.2 Gm. ) doses, three times daily, in capsules, gradually increased until 5 grains are given at each dose, usually suffices. When the cardiac adynamia disappears, a small dose of thyroid, the desiccated gland, ^^ grain (0.03 Gm.) ; strychnine, ]i;o grain (0.001 Gm.), and Blaud's pill, 1 grain (0.06 Gm.), added to each capsule, greatly hasten convalescence. The iron and the adrenal product serve jointly to build up the hemoglobin molecule, a slow process when left to itself. For our knowledge of the action of the use of pituitary extracts in infectious diseases we are mainly indebted to L. Renon and Delille (1907) ; who began their use in 1907. In a recent work in 420 ADRENALS, DISEASES OF (SAJOUS). which the dinical observations of both observers are recorded. Delille ("L'Hy- pophyse et la medication hypophysaire," 1909), referring to grave cases of ty- phoid fever, states that they showed "arterial hypotension, irregularity of the pulse (especially the grave forms), oliguria, insomnia ; while convalescents showed asthenia. hypotension, or at least 'effort hypotension' (Oddo and M. Achard), paroxysmal or continuous ta- chycardia"— all, we have seen, symptoms of hypoadrenia or adrenal insufficiency. They found \]{, grains of pituitary ex- tract (of both lobes) at noon daily ex- tremely efficient ; it counteracted at once the depressed arterial tension, produced diuresis, counteracted insomnia, and greatly improved the general condition. Similar effects were observed in diph- theria and erysipelas. The results in pneumonia do not appear to me to war- rant the use of any adrenal or pituitary preparations early in the case, the first few days of the disease, when the blood-pressure and the fever are high. They should be used only when a low blood-pressure and other symptoms of hypoadrenia are present. The results reported by Delille strengthen this opinion. In advanced tuberculosis no beneficial eft'ect was obtained from this treatment. ACUTE HYPERADRENIA AND ADRENAL HEMORRHAGE.— This condition, which may lead to fatal hypoadrenia by arresting the functions of the adrenals, is generally known un- der the term of "adrenal hemorrhage." The association with hyperadrenia, i.e., excessive functional activity of the ad- renals, introduced here, is important in that it calls attention to the cause of the lethal hemorrhage, viz., abnormally high temperature and blood-pressure. [Just as /jy/>oadrenia appears to me to re- place advantageously "hypoadrenalism" and "adrenal insufficiency," so does "hyperadre- nia" seem to convey more exactly excessive adrenal activity than "hyperadrenalism," which suggests habitual overactivity, besides being less cumbersome than the phase "ex- cessive secretory activity" and others in gen- eral use. C. E. deM. S.] This disorder is, briefly, the result of undue activity of the adrenals. Hyper- emia of these organs occurs normally. i.e., physiologically (owing to their par- ticipation in tlie autodefensive func- tions of the body), in the course of all febrile infections or intoxications. \\'hen these toxemias are .severe this adrenal congestion is increased in pro- portion— sufficiently so in some in- stances to cause rupture of the adrenal vascular elements, and hemorrhage within the organs. An additional cause of congestion in the latter is the abnor- mal rise of blood-pressure which the unusual jiroduction of adrenal secretion entails ; all the vessels of the body being unduly contracted, the adrenal capilla- ries, which are deprived of muscular elements, are overladen with blood and prone, therefore, to rupture. These few facts are necessary to elucidate the definition of the disorder. DEFINITION.— Acute hyperadre- nia is that condition of the adrenals characterized by intense congestion of tlieir vessels, which occurs in the course of severe febrile infections and certain intoxications, and manifested by a high blood-pressure, and in infections, also, by a high temperature. When this congestion exceeds the resistance of the adrenal vessels adrenal hemorrhage oc- curs, causing death when both adrenals are hemorrhagic, in a large proportion of cases, especially infancy and child- hood. [The limitation "certain intoxications" is introduced, because active congestion of the ADRENALS, DISEASES OF (SAJOUS). 421 adrenals is produced only by poisons which cause a marked rise of the blood-pressure, strychnine and quinine, for example. As shown in "Internal Secretions" (vol. i, pages 19 to 55, 4th edition. 1911), the use of such remedies in the course of infections and in- toxications may do harm by increasing the congestion of the adrenals and therefore the chances of hemorrhage. C. E. deM. S.] SYMPTOMATOLOGY AND PATHOGENESIS.— This disorder is relatively common in children, especially in infants ; death occurs, from adrenal hemorrhage, without premonitory symp- toms, except, perhaps, a hemorrhagic rash or purpura — denoting excessive vascular tension — over the body, and a high temperature. The toxemia here has promptly destroyed the adrenals. As a rule, however, more or less marked phenomena, beside those due to the dis- ease from which the child may be suf- fering, and varying considerably with each case, initiate this acute phase of the process, the adrenals being on the border-line of hemorrhage. These may include vomiting and diarrhea, melena, very acute abdominal pain, hemateme- sis, icterus, fever, with hyperpyrexia sometimes immediately before the ad- renal rupture. When the hemorrhage occurs there is more or less sudden col- lapse, a very feeble and rapid pulse, shallow respiration and, perhaps, some bronchial rhonchi, the face being more or less dusky, cyanosed, or even livid, and the temperature subnormal. These phenomena are typical of adrenal insuf- ficiency or failure, the adrenal secretion sustaining, we have seen, general oxy- genation and metabolism and cardio- vascular contractility. Symptomatology of adrenal hemor- rhage as observed in 80 cases: (1) In 46 out of 79 cases there were no appre- ciable signs. (2) In 5 cases there was a voluminous hematoma or abdominal tumor that could be perceived by pal- pation. The diagnosis was made in 1 case only during life. (3) There were peritoneal symptoms in 6 cases, all accompanied by tearing of the cap- sule with hemorrhage. (4) There were symptoms of capsular insufficiency in 8 cases. (5) In 15 cases there was sud- den death, or death after three days at the most, sometimes accompanied by delirium, convulsions, contractures, coma, hypothermia, and syncope. In more than half of the cases, therefore, the hemorrhages remain latent and apparently without effect upon the organism. F. Arnaud (Archives gen. de med.. May, 1900). Series of four cases of hemorrhage into the skin and suprarenal capsules, the interesting features of which were the sudden onset, rapid course and fatal termination. Not one of the patients was over a year old. The history throws absolutely no lighfon the causation of the disease; neither does the question of food ap- pear to bear any relation to it. The presence of hemorrhage in the skin and suprarenal capsules would seem to make it more probable that the disease is some form of toxemia. In two cases the blood from the un- opened heart was examined bacterio- logically wnth negative results. In its extremely rapid and fatal termination the disease somewhat resembled the epidemic diarrhea and vomiting of infants. The general condition of the patients was dififerent. They did not present the sunken eyes and the in- elastic skin wdiich is frequently met with in the epidemic diarrhea, and the cyanosis present in these cases is verjf rarely, if ever, seen in the skin and suprarenal capsules; the fact that Pe3'er's patches were much swollen is interesting. The authors believe that these symptoms are the mani- festations of a special disease, and that the cause of this disease is a blood poisoning of some form, at present unknown. P. S. Blaker and B. E. G. Bailey (Brit. Med. Jour., July 13, 1901). Three cases of sudden death in in- fants, due to hemorrhage into the 422 ADRENALS, DISEASES OF (SAJOUS). suprarenal capsules. The train of symptoms is very definite. A child, previously well, is suddenly seized with acute abdominal pain and vom- iting, the temperature rises, and one of the exanthemata is suspected. No characteristic rash appears, however, though sometimes there is purpura. Convulsions supervene, the patient becomes moribund, and death occurs in a few hours. If the condition is an infection presumably, it is a spe- cial infection of unknown origin. Bac- teriological examination has proved negative in almost every case. Lang- mead (Lancet, May 28, 1904). The microscopic report was as fol- lows : The right suprarenal showed no abnormal appearances. The left supra- renal was much broken up, but there were the remains of hemorrhage in its medullary substance, both in the form of extravasated corpuscles and as gran- ules of pigment. B. G. MorriS^on (Lan- cet, June 6, 1908). Case of a man 35 years old who suc- cumbed in five days to adrenal hemor- rhage. The disturbance was sudden in its onset, with symptoms resembling those of intestinal obstruction : violent abdominal pains, which morphine was powerless to relieve, continued vomit- ing, and absolute retention of gas and feces. Laparotomy was performed and showed the intestinal tract, including the appendix, to be entirely normal. The pain was in no way modified by operation. The temperature rose to 39° C. (102.2° P.), the pulse became extremely feeble, the respiration slow and shallow, and death took place on the fourth day after operation. The autopsy showed bilateral lesions of the adrenals, without other dangers of any kind. The left adrenal gave evidence of a recent and of a former hemor- rhage (the patient had experienced a similar, though less severe, attack a few years before). The condition of the abdomen, slow- ing of the pulse, with temperature re- maining normal, should draw the atten- tion from the intestinal tract to the adrenals. The case also indicates that this syndrome may not be fatal, and, if not fatal, may recur. Brodnitz (Miinch. mcd. Woch., July 26, 1910). In newly born infants suffering from erysifelas and other infections, the writers observed a syndrome con- sisting of vomiting, a green diarrhea with retraction of the abdomen, an erythematous rash, and profound asthenia, leading to algid collapse. The only lesion found at autopsy in such cases was an hemorrhagic dis- tention of the adrenals. Lesne and Franqois (Paris Medical, June 29, 1912). Case of an apparently well boy complaining only of slight fatigue, who suddenly became comatose, the pulse reaching 140 and the tempera- ture 104° F. (40° C.) and died in 36 hours. The autopsy showed initial typhoid lesions in the intestines and a caseous tuberculosis of both adrenals. Mery and Ileuyer (Paris Med., May 30, 1914). In 1 of 2 cases described, the first, occurring in a man 41 years, showed as most prominent symptoms a sub- normal temperature, and slow respi- ration and pulse. Death followed 3 days after a nephrectomy for a pyo- nephrosis. Post-mortem examination showed a number of sharply defined focal necroses scattered throughout the cortical zone of the right adrenal, with degeneration of cells, polynu- clear infiltration, and moderate hemor- rhage of the gland. Many of the capsular vessels were thrombosed, so that this thrombosis of the ves- sels may be a possible cause of the adrenal lesions. E. Moschcowitz (Proceed. N. Y. Pathol. Soc, Oct.- Dec. 1917). Case suggestive of cerebral hemor- rhage. The limbs were rigid, the re- flexes gone, and the pupils distinctly dilated. The face and hands were cyanosed. The temperature was 99° F. (37.2° C). Urine was normal. Cerebrospinal fluid showed no change and gave a negative Wassermann re- action. The patient died lyi hours after admission. The clinical course was thus apoplectiform in type. The necrops}^ was performed within 2 ADRENALS, DISEASES OF (SAJOUS). 423 hours of death. The only organs ex- hibiting any marked pathologic change were the suprarenals. These were almost entirely destroyed, and con- verted into structureless, amorphous, yellowish masses, firm in texture, and considerably larger than the original glands. W. Boyd (Jour. Labor, and Clin. Med., Dec. 1918). In adults, most frequently subjects between 20 and 30 years of age, the at- tack may also be sudden, or preceded by a period of great lassitude or asthenia. In most instances, however, the symp- toms are such as to suggest acute in- toxication or infection, with very severe pain, either in the epigastrium, the ab- domen or below the costal margin, as the pre-eminent symptom. Then follow, in rapid succession, incoercible vomiting and, perhaps, diarrhea, and the signs of adrenal hemorrhage : great weakness of the pulse and rapid decline of the blood- pressure, hypothermia, cold sweats, cold- ness of the extremities, coma and death. This, may, however, be preceded by a typhoid-like state, delirium, convulsions and various perversions of the cuta- neous pigmentation, varying from yel- low to light-brown. In a series of 79 cases collected by Arnaud (1900) death occurred within a period ranging from a few hours to three days. The hemor- rhage may be due to the rupture of a hemorrhagic cvst of the adrenals (treated imder the next heading) and be preceded, therefore, by the symptoms peculiar to this condition. The types of acute insufficiency of the suprarenals are classed by the writer as follows: (1) those of sud- den onset; (2) the asthenic type; (3) the nervous type; (4) sudden death where nothing but a destructive le- sion is found; and (5) cases which occur in hemorrhagic diseases. These types often overlap each other. In the asthenic tj'pe there is only ex- treme asthenia, followed in a few days by death. The nervous type in- cludes those showing convulsions, coma, delirium, or typhoid states. In instances of convulsions the convulsion might well be the cause of the adrenal le- sion. The first type is of particular interest because of its striking simi- larity to acute pancreatitis. The on- set is sudden, "with epigastric pain and tenderness, vomiting, extreme prostra- tion, feebleness and rapidity of pulse, coldness of extremities, lumbar ten- derness, and, at times, diarrhea and abdominal distention, followed within a few days by death." The shock is more profound, the lumbar tender- ness more acute, and the epigastric pain and vomiting less pronounced in adrenalitis than is usually the case in acute hemorrhagic pancreatitis. Attention should be paid to the rela- tive frequency of the condition in the purpuras of childhood and during or shortly after the acute infections; and due consideration must be paid to the apparent insufficiency and in- flammations in the neighborhood of the suprarenals, surface burns, chronic heart or pulmonary disease, and any phenomenon tending to a great in- crease in internal blood-pressure. Lavenson (Archives of Intern. Med., Aug. 15, 1908). In "Internal Secretions" (1903-1907) I called attention to the fact that many drugs influenced the functions of the adrenals, some depressing them, others overexciting them. When from any cause, these organs are debilitated the loss of their influence in the defensive functions of the body causes it to be more easily affected both by drugs, tox- ins, and other poisons. Animals with adrenal insufficiency are more sensitive to intoxication of curare and strychnine than normal animals. A large number of poisons are more active in decapsulated ani- mals than in normal ones. Camus and Porak (Soc. de Biol., June 21, 1913). Sudden death in a man of 47 after 20 c.c. (5 drams) of a 2 per cent. 424 ADRENALS, DISEASES OF (SAJOUS). solution of alypin had been injected into the bladder. The only lesion found was an extensive tuberculous l^roccss in the right adrenal. The writer cites 3 cases from literature in whicl- death followed at once after local anesthesia with cocaine or novo- caine and in both cases the necropsy revealed a tumor in the adrenal medulla. Proskauer (Therap. der Gegenwart, Dec, 1913). Ilypoadrenic subjects tolerate sal- varsan badly. When this potent agent is to be used the signs of hypo- adrenia should be looked for. If these are present the patient should be confined to bed for a couple of days after the injection of salvarsan, and adrenalin be administered sys- tematically during that time. Ser- gent ( Bulletin dc la See. des Hop., Feb. 26, 1914). Toxic doses of all arsenicals of which we have any knowledge pro- duce deiinite pathological changes in the adrenals of guinea-pigs. These changes include congestion, hemor- rhage, disturliances in the lipoid con- tent, cellular degeneration and necro- ses, and reduction in the chromaffin content. The character and severity of the injury produced by different arsenicals vary with the chemical con- stitution of the compounds. From these facts they conclude that ad- renal injury is an important factor in arsenical intoxication. W. H. Brown and Louise Pearce (Jour, of Exper. Med., Nov. 1, 1915). The writer in a comprehensive clinical descri])tion of hemorrhage of the adrenals in the young as observed by him, states that the attack begins with extreme severity, high fever, vomiting, severe al)domina4 pain, cyanosis and often purpura, the pa- tients dying in from 6 to 24 hours after the onset of the symptoms. Friedrichsen (Jahrbuch f. Kinderh., vol. Ixxxvii, p. 1()9, 1918). ETIOLOGY.— That we are deal- ing with a relatively cominon morbid process is shown by the fact that Mattei. Rolleston and Le Conte, in 230 autop- sies in the newborn, found adrenal hem- orrhage in over 100 instances, or 45 per cent., while the proportion in adults is about 1 per cent. To explain the marked predilection of infants to this disorder many theories have been advanced : Weakness of the intra-adrenal vessels, either congenital or due to general dis- orders, such as syphilis, scorbutus, or, again, to lesions of the vascular walls, such as fatty degeneration, aneurism, etc. ; lack of firmness of the medullary portion of the organ, the usual seat of the hemorrhage ; compression by the uterus during labor of the inferior vena cava, thus offering resistance to the blood-streams from the adrenals which enter this great venous channel ; ligation or prolapse of the funis, and other me- chanical factors capable of causing pass- ive congestion of all organs, including the friable and extremely vascular ad- renals. While all these agencies probably cause heinorrhage in a certain propor- tion of cases, the majority are due, as stated above, to some form of intoxica- tion, either toxins or endotoxins of in- fectious origin, or autogenous poisons, such as toxic waste products or auto- toxins of intestinal origin. Some ob- servers have ascribed the morbid pro- cess to a single hypothetical organism, but it has been clearly shown that dif- ferent germs could produce it, including the Staphylococcus aureus and albus (Riesman), the pneumococcus (Hamill and Dudgeon), the pneumobacillus of Friedlander (Litzenberg and White), and others. in adults hemorrhage occurs also, as a rule, as a complication of various dis- eases, some of which, such as septicemia, erysipelas and tuberculosis, are clearly of bacterial origin. Epilepsy, on the other hand, illustrates the class of cases ADRENALS, DISEASES OF (SAJOUS). 42- in which adrenal liemorrhage may be caused by autogenous poisons. In the adult, as shown under the next heading, several of these morbid processes may give rise to hemorrhagic cysts, which may eventually rupture into the abdom- inal cavity. [That a general toxemia is an active factor in adrenal hemorrhage has been demon- strated experimentally. Roger (Le bull, med., Jan. 21, 1894) found that inoculation of the guinea-pig by a pure culture of the pneumobacillus of Friedlander is followed by abundant hemorrhage of the suprarenal capsules, the blood bursting through the great capsular vein and causing necrosis of the elements by mechanical compression. These hemorrhages do not occur in the rab- bit. Langlois (Le bull, med., Feb. 7, 1894) saw hemorrhages produced by the pyo- cyaneus bacillus. Pilliet (Le bull, med., Feb. 7, 1894) has also observed such hemorrhage after intoxication by essence and nitrate of uranium. C. E. de M. S.] The adrenals are exceedingly vas- cular, and at times are subject to emporary passive engorgement. An- other cause of hemorrhage is unques- tionably bacterial invasion, and sev- eral hemorrhages of considerable size have been reported as due to this cause. The hemorrhage may be also due to toxemia from irritating chem- ic-il poisons. In animals who have been injected for experimental pur- poses, with sera or antitoxins, as, for example, that of diphtheria, severe congestions and, occasionally, hemor- rhages have occurred. A. J. M'Cosh (Annals of Surg., June, 1907). Instance in an epileptic who died during an attack of enteritis, and in whom the autopsy revealed recent extensive hemorrhage in both ad- renals. This seems to be a rare cause of death in adults, though not so uncommon in children. The reported case is one of Arnaud's asthenic type, probably due to circulatory failure from sudden removal of the tonus, producing secretion of the supra- renals. J. F. Munson (Jour. Amer. Med. Assoc, July 6, 1907). Case of adrenal hemorrhage and acute edema of the lungs in the course of convalescence from acute nephritis due to erysipelas. The patient, a woman of 35 years, died suddenly on the fourth day of the nephritis, which had been brought on by exposure to cold. The autopsy showed, besides the evidences of pulmonary edema and intense acute nephritis, great distention of the adrenals by hemor- rhage into them, with complete de- struction of the medullary substance. Loederich (Le bull, med., July 8, 1908). From an extensive experience in autopsy work in the newly born, the writer believes that hemorrhage into the suprarenals is very common, and that the evidence is sometimes micro- scopic instead of macroscopic. He has found some degree of hemor- rhage in infections due to the strep- tococcus, staphylococcus, pneumococ- cus. Bacillus pyocyanens, the colon bacillus and a micrococcus he was unable to classify. We may have in- fections with the pneumococcus with- out any evidence of pneumonia. S. M. Hamill (Jour. Amer. Med. Assoc, Dec 5, 1908). Hyperplasia of the adrenal is an al- most constant lesion in arteriosclerosis associated with chronic interstitial ne- phritis and left-sided hypertrophy, and it occurs with almost equal fre- quency in arteriosclerosis with chronic nephritis of the parenchynjatous type ; it is also a frequent lesion of arterio- sclerosis without nephritis and of ne- phritis without arteriosclerosis. Adre- nal hyperplasia is, consequently, prob- ably the result of some factor active in a period of life in which these affections are most frequent. T'le adrenal lesion consists of increase of connective tis- sue, round-cell infiltration, increase in the thickness of the vascular wall and hyperplasia of the adrenal cells proper. Pearce (Jour, of Exper. Med., Nov., 1908). PATHOLOGY. — An important function of the adrenals is to destroy products of metabolism. This was first 426 ADRENALS, DISEASES OF (SAJOUS). shown by Abelous and Langlois, whose views have been confirmed by many ob- servers. Subsequently this function was found to apply to bacterial toxins. The prevailing view as to the pathogenesis of adrenal apoplexy is that, as a result of the active congestion of the adrenals incident upon infection and excessive functional activity and the high blood- pressure resulting therefrom, or passive congestion due to factors which prevent the free passage of blood out of the or- gans, such as pressure upon the adrenal veins, the inferior vena cava, etc., the capillaries become engorged and yield, thus causing a more or less diffuse inter- stitial hemorrhage. In some instances the entire adrenal parenchyma is de- stroyed, and the organ is more or less dilated by the blood accumulated in it, and may thus form a brownish or red- dish-blue mass, varying in size from that of a small walnut to that of the under- lying kidney. In other cases the organ ruptures, the blood flowing into the peri- toneum or tlie abdominal cavity. Both adrenals are involved in the morbid pro- cess in most instances. Other organs, the lungs, the pleura, and skin in par- ticular, may also be the seat of hemor- rhage, the purpura witnessed in a large proportion of cases being naught else than a punctiform hemorrhage into the cutaneous tissues, due to excessive vas- cular tension. Death may be due to these hemorrhages or to the annihilation of the functions of the adrenals. Small ecchymoses into the adrenals occur frequently in the various infec- tious diseases and are to be considered toxic in origin. Hemorrhagic infarc- tion of both adrenals often leads to peritonitis and collapse and may result in death. It may, however, occur with- out any of these sequences. Large hem- atomata may be found in the adrenals. Hemorrhage into these glands may also occur under the following circum- stances : traumatic influences (under this class is found the form seen in the newborn); hemorrhagic diathesis; thrombosis of the suprarenal veins, ' which is the most common cause ; and bacterial capillary embolism, which oc- cupies the second rank. The thrombi can affect the trunk or the tributaries of the suprarenal veins; they can occur in both or only in the ri jht organ ; they are to be regarded as marantic thrombi, occurring, as a rule, only in individuals suffering from some form of chronic disease. The peculiar anatomical dis- position of the vessels favors their formation. A primary suprarenal dis- ease does not precede these cases. Under the cases of bacterial capillary emboli are included those in which neither clinically nor anatomically can septic disease be observed. Bleeding into the adrenals may lead to atrophy of the organ. M. Sinuuonds (Vir- chow's Archiv, Nov. 3, 1902; Med. News, Dec. 27, 1902). Acute hyperadrcnia and adrenal hem- orrhage in the infant may also be due to toxemia. While the fetus is in utero its waste products are transferred to the maternal blood and converted therein into eliminable products. When its birth occurs it is left to its own resources, and if it is unable fully to break down its waste products these accumulate in its blood. Its waste products — and this ap- plies as well to certain toxins, including those enumerated above — excite power- fully both tlie adrenal system and the vasomotor center (hence the flushing following a copious meal). If the adre- nal system can thus be made to prevail, the wastes (or toxins) will be gradually destroyed, and the vasomotor center will not be abnormally excited. If it is not, the wastes accumulate, and the vaso- motor center being powerfully stimu- lated, the vascular tension and the blood- pressure become intense ; this being fur- ther enhanced by the excess of adrenal ADRENALS, DISEASES OF (SAJOUS). 427 secretion produced, the pressure be- comes such that the adrenal tissues, al- ready overburdened with blood as a feature of their overactivity, yield — along with many cutaneous capillaries, as witnessed by the hemorrhagic pur- pura. Examination of the adrenals in 16 cases of diphtheria, 10 of variola, 23 of lobar- and broncho- pneumonia, 5 of typhoid fever, 1 of tetanus and 4 of streptococcus infection. The glandular cells were profoundly al- tered. There was also hemorrhagic extravasation into the stroma, in which the poljnuclear neutrophilic leucocytes are especially alnindant. True abscess formation occurs chiefly in the prolonged infections of variola and typhoid fever. No peculiar alter- ations were observed as the result of special infections and the changes in general were common to all the cases examined. A pericapsular scle- rosis, cortical and central, was pres- ent in most cases. This chronic lesion is not due to the acute process, but is to be regarded as the result of previous repeated or continued infec- tions. The writers regard the ad- renals as possessing an important function in the resistance of the organism to infection. Oppenheim and Loeper (Archives de med. exper., Sept., 190n. Case of a male infant, four days old, who was born after a normal labor. On the fourth day after birth the infant ceased to pass urine and after total suppression for twenty- four hours it died. At the autopsy the chief interest centered in the suprarenal bodies; the left one was replaced by a tumor the size of a hen's egg and the right one pre- sented a tumor as large as a cherry at its apex. The structure of both tumors was identical. l)oth showing a hypoplasia of the fascicular zone fol- lowed by marked fatty changes and necrosis. In the case of the growth in the left suprarenal bodj% liquefac- tion of the necrosed central portions gave rise to a cyst which was filled with cell debris. Both growths were considered to belong to the group of adenoma. A. S. Warthin (Archives of Pediatrics, Nov., 1901). Results obtained by inoculating rabbits and guinea-pigs with cultures of various micro-organisms. Tlie micro-organisms used were diplo- cocci, typhoid liacilli, bacterium coli. Staphylococcus aureus, streptococci, anthrax bacilli, and diphtheritic bac- illi. In the experiments with active cultures there was always great hy- peremia of the suprarenal bodies and in the more active cases there were hemorrhages. E. Frederici (Lo Sperimentale, Iviii, Fasc. 3, 1904). Common pathological cnanges found in the suprarenals are hemorrhage, which converts the medulla of the organ into a pulpy mass, and em- bolism of the suprarenal artery, whereby the entire organ is des- troyed. Occasionally, one or both organs will be converted into the large bluish tumors, whose contents are fluid blood. This is especiallj^ common in the newly born, and many believe that the motions neces- sary for artificial respiration are the real cause. In a number of cases ob- served by the author, however, arti- ficial respiration was not resorted to, and it is likeh' that severe labor, par- ticularly if the child is in the breech position, will furnish the necessary trauma to rupture the friable supra- renal tissue and thus give rise to a hematoma. If both organs are af- fected the symptoms are those of Addison's disease, and death rapidly sets in. S. Oberndorfer (Wiener klin. therap. Woch., June 18, 1905). Conclusions based on a study of 119 cases including 2 personal cases: 1. Hemorrhage of the suprarenal cap- sules is more common than hemor- rhage in the other viscera. 2. This is due primarily to the close relation of the adrenals to the vena cava, mak- ing congestion easj-, and to the peculiar anatomical construction which favors hemorrhage. 3. A weakness of the vessel walls, either normal deli- cacy or pathological alteration favors 428 ADRENALS, DISEASES OF (SAJOUS). the rupture. 4. The place of election of the hemorrhage is usually in the internal cortical zone because of its vascularity and the anatomical ar- rangement of the vessel. 5. The bleeding always follows active or passive congestion. 6. I^assive con- gestion may be caused by difficult labors, obstetric operations, throm- bosis, or. in short, anything that would favor venous stasis. 7. Active congestion is induced by infection or any toxemia which incites hyperemia by a superactivity of the gland. 8. The findings of the pneumobacillus of Friedlander in the 2 cases per- sonally reported and other bacteria in 5 additional cases prove beyond question tliat infection is a cause of adrenal hemorrhage. 9. Death re- sults either from loss of blood or an interference with the physiological function of the gland. J. C. Litzen- berg and S. Marx White (Jour. Amer. Med. Assoc, Dec. 5, 1908). TREATMENT.— The literature of the subject is suggestively silent on the prevention and treatment of this condi- tion. The foregoing conception of its pathogenesis, however, opens a greater field in this connection. As to prophyla.xis, it must be borne in mind that acute hyperadrenia is present when the blood-pressure and the febrile process are abnormally high. Antipy- retics are worse than useless, since they further increase the blood-pressure and through this fact the danger of adrenal congestion, which may lead to hemor- rhages. The physiological saline solu- tion offers, on the other hand, all desir- able qualities. It does not, as argued theoretically by some authors, increase the vascular tension, even if injected intravenously, as shown by the experi- ments of Sollmann (Archiv f. exper. Path. u. Pharm., Bd. xlvi, S. i. 1901). Briggs (Johns Hopkins Hosp. Bull.. Feb., 1903), and others, any excess of fluid leaves the vessels at once. By re- ducing the viscidity of the blood, saline solution tends to relax the blood-ves- sels ; by increasing its osmotic proper- ties it facilitates greatly the penetration of the plasma into the lymphatic chan- nels, thus further reducing the vascular tension. The bactericidal and antitoxic properties of the blood are not reduced in the least by this procedure; there is considerable evidence available to show, in fact, that they are enhanced (see "In- ternal Secretions," 4th ed., vol. ii, p. 1367, 1911). Saline solution, therefore, should be used intravenously in emerg- ency cases ; subcutaneously in threaten- ing cases, and per rectum in all cases in which there is any likelihood whatever that adrenal hemorrhage might occur. If employed from the onset of all infec- tions, as I suggested in 1903, the blood- pressure would probably never be raised sufficiently to endanger the adrenals. As to drugs, we have several at our disposal which lower the blood-pressure. In emergency cases nitrite of amyl by inhalation, with nitroglycerin (or, in children, the sweet spirit of niter) to sustain the effect, ai)pcars indicated. Chloral hydrate has been used advan- tageously by J. C. Wilson in certain ex- anthemata, to subdue the cutaneous dis- comfort and as a sedative; as it is also a vasomotor depressor, it might also serve advantageously in all but infants in whom the respiratory mechanism is de- fective. Veratrum viride suggests it- self as another useful agent of this class. Of all measures, however, the saline so- lution is much to be preferred. When the hemorrhage has occurred the lethal i)henomena are of such short duration in most cases as to have sug- gested, we have seen, the term "adrenal apoplexy." In a fair proportion of cases, however, the hemorrhage causes sudden hypoadrenia. The treatment of ADRENALS, DISEASES OF (SAJOUS). 429 this condition is that indicatetl in the emergency cases of terminal hypoadre- nia (see page 413). If the hemorrhage has not been too extensive the chances of recovery will be greatly increased by the use of adrenal or pituitary prep- arations, the latter owing its proper- ties, in my opinion, to the adrenal chromaffin substance the pituitary con- tains. These agents will help to sustain oxidation and metabolism while the adrenal lesion is undergoing resolution. Although the adrenals have been regarded as impervious to X-rays, the writers found that hyperplasia with accompanying overactivity of the glands is reduced by them, owing to a retarding influence upon tissue proliferation. They obtained a reduc- tion of blood-pressure, as shown by Pachon's sphygmo-oscillometer, fol- lowing irradiation of the adrenals. Out of 16 cases, the pressure re- mained high in only 1. Zimniern and Cottenot (Arch, d'elect. med., June 7, 1912). The writer analyzes the recent literature on hemorrhage in the suprarenals in children. When it is actual apoplexy, it is inevitably fatal, but with anything short of this, with low blood-pressure, intermittent cyanosis and asthenia, large and re- peated doses of adrenalin are called for, watching over the effect by the arterial pressure. He recalls the in- teresting case of Vollbach's in which a girl of 15 presented purpura a year before developing Addison's disease. Comby (Arch, de Med. des Enfants, Dec, 1918). HEMORRHAGIC PSEUDO- CYSTS OF THE ADRENALS.— In most instances hemorrhagic blood- cysts are the results of acute hyperad- renia in the course of some infection or intoxication in which the adrenal hem- orrhage has been limited to a small area, which eventually develops into a cyst. SYMPTOMS.— These growths may give rise to no symptoms, other, per- haps, than a sensation of weight, until quite large, when pain supervenes. This is at first indefinite, though most marked in the region of the tumor, in the right or left loin, or in the upper portion of the abdomen and loin. The neuralgia-like pain becomes increas- ingly severe, and radiates in various directions, especially toward the hip and thigh of the corresponding side, and is subject to exacerbations, which may be very severe, especially after meals. Epigastric pain and vomiting — which affords relief — occur in some cases, especially during these exacer- bations of suffering. While such a cyst or adrenal hema- toma may attain a large size, the fact that the opposite adrenal remains uninvolved practically excludes the production of symptoms of altered adrenal function, the signs of the tumor being merely a sensation of weight and pain due to pressure on surrounding sensitive structures. Subsequently, the patient may sud- denly begin to fail, losing weight and developing dyspnea, polyuria, hema- turia, and even slight bronzing. The termination is usually through rup- ture into the abdominal cavity. Sajous (Da Costa's Therapeutics, 1918). The tumor may manifest itself at first merely by enlargement of the abdomen. The bulging then becomes more clearly defined on one side or the other (this variety of growth being almost invari- ably unilateral), imder the lower ribs, which may be pushed outward if the growth is sufficiently large, or below their free border, i.e., between them and the superior spine of the ilium. If the tumor, which grows downward and for- ward, is sufficiently below the ribs to be palpated, it is usually found globular, or 430 ADRENALS, DISEASES OF (SAJOUS). oval, smooth and tense, though elastic, to the touch. Fluctuation may also be elicited. In some cases it is immovable under palpation, though it may, at first, follow the respiratory movements. Nor can it be grasped as is sometimes possi- ble in renal tumors; if small, the tumor is movable, either upward or downward, but this mobility gradually decreases as the tumor develops. The growth is sometimes sensitive under pressure. At first, several years, perhaps, the patient may appear normal in every other respect, be well nourished, ruddy, etc. With comparative suddenness, how- ever, he begins to fail, losing flesh rap- idly, all the other symptoms mentioned, to which dyspnea and a sense of con- striction about the chest is added, be- coming more severe. If the cyst does not rupture, polyuria, hematuria, and even slight bronzing may appear. It is probable, however, that this train of phenomena is witnessed only in a very small proportion of cases, rupture and hemorrhage constituting the "adrenal hemorrhage" in adults treated under the preceding heading, being the outcome in practically every instance. Adrenal hemorrhage in the newborn is probably not uncommon, but in the great majority of cases there are no symptoms to indicate the occurrence of such a lesion, and the hematoma is quickly absorbed. It is equally difficult to understand why in adults these hemorrhages should occur. The deep situation of the adrenal bodies would seem to be sufficient protection from in- jury, except that of the severest char- acter, and yet in a certain proportion of these cases the cause has aparently been a trauma. A. J. M'Cosh (Annals of Surg., June, 1907). [This abstract indicates the drift of the prevailing conception of the pathogenesis of these growths. While local lesions are as- cribed to the concomitant disorder, the ad- renals, being supposedly affected directly by the toxin or poison that may be present, are thought to explain some cases, others require, it is believed, some form of traumatism. It is to the excessive blood-pressure pro- duced by the toxin that the vascular rup- tures to which the hemorrhage is due should be ascribed. C. E. de M. S.] DIAGNOSIS.— The symptomatol- ogy of adrenal cyst, apart from the loca- tion of the tumor, does not present, as just shown, very characteristic features. The location of the pain sometimes sug- gests intercostal neuralgia; but inas- much as jiain occurs only when the growth is large, percussion and palpa- tion will reveal the presence of a tumor. In neuralgia the pain is also apt to be localized, thus distinguishing it from the radiating pain of adrenal cyst. The sud- den onset of severe pain may be taken for acute pancreatitis. The location of pain and tenderness in the upper left ab- dominal quadrant, the subnormal tem- j)erature and the early lethal trend — death occurring sometimes within three days— ^clearly ]K)int to the latter dis- ease. Pancreatic cyst is also difTeren- tiated by its location and its association with glycosuria, stearrhea, and imper- fect digestion of fats and albuminoids. Hydatid cyst of the liver, another source of confusion, is attended by the presence of biliary pigments in the urine, the ap- pearance of cysts in the stools and vom- ited matter, and with obstruction phe- nomena. Cancer of the spleen may be recognized by the more nodular outline of the growth and the cachectic phe- nomena. Hydatid cyst of the spleen is usually associated with hydatid cysts elsewhere, and may be accompanied by the presence of booklets in the excre- tions. Puncture of the growth should be carefully avoided when there is any suspicion whatever that an adrenal blood-cyst is present. Renal cysts are ADRENALS, DISEASES OF (SAJOUS). 431 more easily palpated bimanually, and are usually freely movable. Cysts are due to the tendency of the adrenals to hemorrhage. Four- teen cases are reported in literature, of which 7 were post-iiiortein reports or complications of other adrenal tumors. The other cases were well- defined blood-cysts of the adrenal glands. The author reports the case of a waitress witli a history of right side pain of a cramping nature, on several occasions — she thought 5 or 6. A large tumor was present in the upper right abdomen; shock, pain, difficult breathing, rapid pulse. Operation showed a cjst covered with peritoneum attached to the back above the right kidney. All organs were displaced by the cyst, which was as large as an adult head. The pa- tient recovered, and was well 1 year later. H. E. Fearce (Trans. West. Surg. Assoc; Surg., Gynec. and Ob- stet., Feb., 1917). ETIOLOGY.— Adrenal blood-cyst has been ascribed to many morbid con- ditions. Acute intoxications, especially diphtheria, typhoid fever, burns, osteo- myelitis, hepatic abscess and tuberculo- sis, have been regarded as initial factors of these growths, a small cyst formed during the active stages of these dis- eases, or, as a complication thereof, gradually increasing in size until the foregoing phenomena or adrenal hem- orrhage occur. In the light of the data submitted in the foregoing pages, they are merely after-efifects or complica- tions, in other words, of the damage done to the adrenals during an acute febrile toxemia. Atheroma of the adrenal arteries is also regarded, and doubtless justly, as a source of initial lesions, but it is prob- able that cerebral lesions of the same kind and apoplexy, which have been considered by some authors as etiolog- ical factors, are merely concomitant lesions due to general arteriosclerosis. Thrombosis of the adrenal vein by blocking the efiferent circulation has also been incriminated, while traumatism is known to have started the morbid proc- ess in at least two instances. PATHOLOGY.— While older in^ vestigators, including Klebs, Virchow and Heuschen, considered these growths as retention cysts, similar to those formed in the thyroid, and thus termed them "struma adrenalis," the prevail- ing view at the present time is that a small hematoma or an acute congestive process- — though erroneously, in my opinion, ascribed to local intoxication — initiates the growth. As the latter in- creases in size the adrenal structure is gradually destroyed and the content is no longer — unless a recent hemorrhage has occurred — merely blood, but a tnore or less fluid magma of detritus, broken- down blood- and tissue- cells, flakes or fibrin, cholesterin crystals, etc., which may be dirty yellow, greenish or brownish in color. Microscopically, the walls of the cyst, which vary from %g to Ys inch in thickness, are composed of fibrin tissue ; the inner aspect shows shreds or remnants of the adrenal cortex. Certain thickened portions of the capsule and what semiorganized clots the cyst may contain may be found to include small cysts, chalky deposits. These growths sometimes become very large — as large as an adult head in a case of Chiari's — and contain several pints of blood or liquefied blood and tis- sue elements. PROGNOSIS.— The fact that this growth is practically always unilateral, and that the loss of one adrenal does not compromise life, as does removal of both organs, make it possible to remove the growth with safety. The frequent instances of severe collapse and shock 432 ADRENALS, DISEASES OF (SAJOUS). that have followed these operations sug- gest that the operative prognosis can- not but be improved by resorting to those surgical procedures which will en- tail the least possible handling of the intraperitoneal organs and of the sym- pathetic ganglia, all of which are well known to produce shock readily by re- flex action. TREATMENT.— The treatment is, of course, entirely surgical. The cyst may be removed through either an ab- dominal or lumbar incision. In accord with M'Cosh's advice, whicli a review of the operative results recorded fully sustains, preference should be given to the lumbar incision. The a])proach is more direct; it avoids the handling of the intraperitoneal organs, which must necessarily take place if the tumor be reached through the abdominal incision, and it affords the most direct route for drainage. In the average case, an ob- lique incision from behind downward and forward below the last rib. which has been found most convenient for ex- tirpation of the kidney and ureter, is as ap])licable here. If much space is neeredominated that the fluid which escaped from the glomeruli was albuminous, but that the albumin w^as absorbed during the pas- sage through the healthy renal tubules, diseased tubular epithelium being un- able to absorb the albumin. This has not been proved, however, and most modern authors believe that albumin is not contained in the urine coming from the glomeruli, except when these are diseased or when the pressure of blood in the glomeruli is abnormally great. Runeberg, on the contrary, is of the opinion that albuminuria is caused by low pressure of blood, and supports this opinion by experiments with animal membranes, but experiences with dead membranes cannot be regarded as con- clusive for the action of the living kidney. * \'on Noorden and other authors re- gard the tubular epithelium as the unique source of albuminuria. These epithelial cells are subject to successive disintegration: when this is minimal, and successive traces, only, of albumin are found in the urine, the albuminuria is physiological ; when the disintegra- tion of the tubular epithelial cells is augmented and hastened by disease, a morbid albur(iinuria takes place. In his opinion, this theory is supported by the fact that nucleoalbumin, of which the protoplasm of the cells undoubtedly is the source, is always found in nor- mal urine. Benign albuminuria depends, ac- cording to the writer, on a vagatonia which is itself due to a reduced tonus of the sympathetic caused by aplasia and insufficiency of the chromaffin system. In vagatonia the renal ves- sels are constantly dilated because of the decreased tone of the sympa- thetic. When, in a person so affected, a greater quantity of adrenalin is secreted because of any reason what- ever, the reduction of tone of the sympathetic becomes still greater, and consequently the dilatation of the renal vessels becomes so great as to give rise to renal stasis and so to an albuminuria. C. v. Dziembovvski (Berl. klin. Woch.; Corresp. blatt f. schweizer Acrzte, Jan. 19, 1918). Senator considers physiological al- bumiimria in the same light as physio- logical glycosuria, and, among the causes that give rise to it in susceptible individuals, he mentions : severe exer- tion of the lower extremities, eating and digestion of hearty meals, men- struation, cold baths, p.sychical excite- ment, etc. lie deems albuminuria pathological only when it does not disappear promi)tly on the cessation of the particular stimulus that caused it. Physiological and allied forms of albuminuria are attributed to con- genital predisposition of the individ- ual to disease of any organ which directly or indirectly may influence the elimination of albumin. The influence of exertion was shown on 528 soldiers by the writers. Of these 56, or 10.6 per cent., had albuminuria. The amount of albumin was small in the great majority. To determine the influence of work and rest on the excretion of urine, the latter was examined immediately after work, and in the morning after a night's rest. It was found to be present in 11.5 per cent, after work- ing, in 7.9 per cent, after rest. M. Laber and P. Lauener (Corresp. Bl. f. schweizer Aerzte, July 24, 1915). In soldiers the writers found com- plications in the kidneys directly after acute infectious diseases in 17 per cent, of the men examined, irre- spective of whether the men had been serving at the front or had never reached the trench line. In 6 of 18 men the albuminuria had developed ALBUMINURIA (LEVISON AND ERLANDSEN). 465 after acute tonsillitis. There was a history of some old acute infectious disease in 40 per cent, of the eighty men from the front and in 50 per cent, of the thirty others. In 22 per cent, there was primary nephritis oc- curring in previously healthy men. In two of the men the albuminuria developed after antityphoid vaccina- tion. Chronic albuminuria which may be well borne in civilian life is ex- tremely liable to give trouble under the stress of military life. Merklen (Annales de Med., May-June, 1918). From a pathological point of view the causes of albuminuria may be divided into three groups: 1. Disturbances of circulation. 2. Changes of the tubular epithelial cells or of the walls of the blood-vessels of the kidney. 3. Changes in the composition of the blood. 1. All disorders of circulation capa- ble of causing a venous renal congestion will increase the blood-pressure in the capillaries of the kidney, and thus give rise to a transudation of albuminous liquid; when the congestion is very great the urinary tubules may even be compressed and the escape of the urine rendered difficult. When this is the case and when, also, the supply of arterial blood is diminished, the tubular epithelium will be damaged, and the first result of all this is albuminuria. It is very improbable that arterial con- gestion ever produces albuminuria, al- though the experiments of Munk and Senator tend to prove the contrary. Leube found in the early stages of aortic insufficiency, not accompanied by cyanosis, edema, etc., a slight albumi- nuria. Pathological examination of the kidneys showed the walls of arteries and capillaries much thickened. He makes these changes and their conse- quences responsible for the maltnutri- tion of the kidney and its result : albuminuria. 1- 2, Changes of the tubular epithelia and the walls of blood-vessels of the kidneys may, as already stated, be due to disorders of circulation, but they may also be caused by different poisons and toxins. When albuminuria is chiefly caused by degeneration of the tubular epithelia, their protoplasm dissolves in the urine, and nucleoalbumin in great quantity is contained in it, combined with serum-albumin and globulin. Menge and Schreiber noted albumi- nuria in several cases in which the kidney had been palpated bimanually, as a result of the circulatory changes produced during the examination. This procedure has been used by Schreiber in the diagnosis of doubtful cases of floating kidney. 3. When the composition of the blood is altered, the urine often becomes albuminous. This can be proved ex- perimentally by injecting egg-albumin, soluble casein, hemoglobin, etc., into the veins of animals; the quantity 6f albumin excreted after the injection will generally exceed the quantity in- jected. Similar results may be obtained by the injection of peptone and propep- tone, whereas the albuminates are gen- erally inoffensive. Ingestion of a very large quantity of egg-albumin is liable to provoke albuminuria. Semmola has tried to prove that albu- minuria is always caused by changes of the blood characterized by abnormal diffusibility of its proteids, and, in his opinion, the pathological changes in the kidneys are consecutive to the albumi- nuria. Though his theory is not gener- ally accepted, Rosenbach has adopted it for the albuminuria which is not caused by nephritis, and regards it in such cases as a salutary and regulating process, if such can occur at all. In most clinical cases different causes -30 466 ALBUMINURIA (LEVISON AND ERLANDSEN). are simultaneously active, and it is generally very difficult to determine which is the preponderating etiological factor. L. Williams ascribes the ma- jority of cases of albuminuria either to altered blood states or to failure in the normal vasomotor mechanism. The majority of the cases arc due to either altered blood states or to failure in the normal vasomotor mechanism. This failure may man 'f est itself in one or two directions. In the first, chiefly by some means so far undiscovered, the blood-pressure in the splanchnic area arises and is maintained at a suffi- ciently high level to induce a renal plethora and consequent albuminuria. Of such are the cases of hyperpiesis, as in the instance quoted. In the sec- ond place, owing to a local or general vasodilatation, the blood-pressure in the splanchnic area falls to the point at which a renal stasis is induced. Of such are the cases of cyclical, postural, and athletic albuminuria, of which also instances are cited, cases which, for the most part, occur in young adults in whom the vasomotor response is either undeveloped or for some reason is in- adequate. Having regard to these facts, the writer ventures once more to insist not only that, of itself, albumi- nuria affords no evidence of renal dis- ease, but that, of itself, it does not present even a reasonable suspicion of the existence of such disease any more than, of itself, dyspnea presents a rea- sonable suspicion of cardiac disease. L. Williams (Clin. Jour., Apr., 1908). It is, nevertheless, true that traces of albumin, and even a rather considerable amount of it, may be found in the urine of persons otherwise healthy and pre- senting no symptoms of disease of the kidneys or of the organs of circulation. Many clinicians, therefore, admit that albuminuria may be regarded, in some cases, as physiological; this is, however, contested by many. Case in which for over twenty years the patient had been passing large quantities of albumin in the urine, 3 grams per liter. Microscopic examina- tion revealed no casts or corpuscles, and there was nothing to suggest renal trouble. The heart was normal in size, the sounds were normal, blood-pressure was in the limits of the normal, and there was little or no arterial thicken- ing. The patient has maintained his usual high standard of health, and, al- though he had always been thin and spare, he is very tough. The most re- markable feature of the case, however, is that all the members of the patient's family exhibit the same peculiarity. They are all perfectly well, and, con- sidering the age the parents have at- tained (87 and 78 respectively), such a case as this should have an important bearing on the question of rejection or "loading" of candidates for life insur- ance. Fergusson (Brit. Med. Jour., Mar. 19, 1910). Virchow described a physiological albuminuria in infants, occurring in the first days of life, and explained it by the sudden changes of circula- tion taking place immediately after delivery. Flensburg and Sjoquist have shown that albuminuria regularly occurs in the first days of life, and that the urine also contains an extraordinary quantity of uric acid crystals; prob- ably the albuminuria is then due to the irritation of the kidneys caused by these crystals. Ebstein and Nicolaier have shown experimentally that when the kidneys are forced to excrete a surplus of uric acid which cannot be dissolved, but goes to the bottom in the form of crystals, the urine commonly contains albumin and sometimes even blood. Gull found a certain form of physio- logical albuminuria in adolescents about the age of puberty, especially in weak and pale individuals. Other authors, among whom is Quain, have ALBUMINURIA (LEVISON AND ERLANDSEN). 467 noticed that this condition is quite frequently associated with masturba- tion. Lommel found that 19 per cent, of young men (14 to 18 years old) suf- fered from albuminuria without hav- ing nephritis. The albuminuria had an intermittent character and was orthostatic in type. Dunhall and Patterson and Collier found albuminuria (0.2 to 15 per cent.) after severe exercise (such as rowing and running in races) also in healthy subjects. Albuminuria is of fairly constant occurrence in patients who have acute or chronic suppuration. If an abscess is deep and under consider- able pressure, albutninuria is more likely to occur. If the abscess is drained, the albuminuria disappears. Marcozzi (Folio Urologica, Feb., 1914). The writer had several cases that showed a transient albuminuria after lavage of the stomach, although nothing of the sort was present be- fore. Schiflf (Wiener klin. Woch., May 28, 1914). The writer examined the urine of every soldier admitted to the sur- gical hospital in his charge, a total of 3210 men. Albumin was found in 13 per cent, but never in large propor- tions. Engel (Deut. med. Woch., Nov. 23. 1916). PHYSIOLOGICAL CYCLICAL, ORTHOSTATICAND ORTHOTIC ALBUMINURIA.— The question of physiological albuminuria in adults has been much discussed during the past few years and has particularly engaged the interest of the medical men employed in insurance work. Stirling was the first to call atten- tion to intermittent albuminuria in children in connection with the posi- tion of the body, and he styled it "postural albuinintiria." The writer holds that this is the best name for it. as neither the orthostatic nor the lordotic attitude ever induce it except in the predisposed. Of the 204 chil- dren examined, albuminuria could be induced by lordosis alone in only 3 per cent., and by a change from the seated to the erect posture (orthos- tatism) only in 1.3 per cent. Both together, the 'children not keeping still, induced albuminuria only in 1.6 per cent. The findings in the vari- ous groups listed show that the rest- lessness of children responds to a physiologic demand, and that chil- dren should not be expected to sit still in school. The school desk should be arranged. Jeanneret (Arch de Med. des Enfants, Sept., 1915). A study of 5 cases of orthostatic albuminuria led to the conclusion that it is a general systemic disturb- ance, manifesting itself in faulty de- velopment, as shown by a general visceroptosis, a "drop heart," a gen- eralized muscular and visceral atonia, which is known to be associated with varying degrees of vasomotor in- stability. The symptoms so com- monly complained of, such as head- ache, lassitude, constipation and loss of weight, are the natural results of physical conditions. The increased lordosis that is usually present is re- garded as a symptom due to the faulty muscular development and tone of the lumbar muscles. The low pulse-pressure is undoubtedly the cause of the albuminuria rather than a mechanical interference with the venous return from the kidneys. Mason and Erickson (Amer. Jour. Med. Sci., Nov., 1918). It is characteristic of physiological albuminuria that the quantity of albu- min is generally small and that the excretion is, in most cases, intermit- tent, or cyclical. Leube, Pavy, Fiir- bringer, Klemperer, and many other authors have studied this condition. Pavy introduced the denomination "cyclical albuminuria" for the cases in which the albuminuria ceases and returns at regular intervals. 468 ALBUMINURIA (LEVISON AND ERLANDSEN). Stirling ascribes cyclical albumi- nuria to a sudden shock from the blood-pressure upon assuming the upright position on arising, but Rudolph showed that albumin also appeared in the urine when the up- right position was assumed very slowly. Pavy likewise insists upon posture as the invariable cause of cyclical, or in- termittent, albuminuria, the excretion ceasing when the subject is in the re- cumbent position and going on only when he is walking or standing. The cycles are commonly completed within the day, but in a case narrated by Klcm- perer there were two cycles, the maxi- mum of albuminuria taking place in the forenoon and afternoon. Hauscr concludes that tliesc cases can always be traced back to an uncured nephritis or to some acute infection (notably scarlatina), and ]nits no cre- dence in a functional disorder. In other words, he always considers cyclical al- buminuria as the expression of some pathological factor. Oswald attributes all forms of albu- minuria of adolescence to irritation of the renal epithelium. Moritz ascribes cyclical albuminuria to some insufficiency of the circulatory apparatus, having observed that the in- creased blood-pressure which normally occurs after moderate exercise is fol- lowed by abnormally low pressure in individuals that are subject to cyclical albuminuria. The diagnosis of physiological albu- minuria ought not to be made except in cases when persons presenting no other symptoms of disease excrete, constantly or intermittently, a urine containing a scanty quantity of albumin, but no morphotic elements and especially no casts. The centrifugal apparatus, now in general use, will certainly contribute to restrain the number of these cases. The urine should be obtained by catheterism in all doubtful cases. The prognosis is generally considered good (Broadbent, Beck, Dukes, Ties- sier, Posner). Nevertheless it is still justifiable for life-insurance examiners to be cautious in accepting persons suffering from albuminuria. It is no longer justifiable for life in- surance and other such examiners to take the serious view hitherto ac- cepted by most clinicians of physio- logical albuminuria. When it is found that the excretory function is being properly performed; that the sul)Stances normally gotten rid of through the kidneys are not being re- tained in the organism, and that the albumin in the urine may be dimin- ished by lessening the hydrostatic pressure upon the renal capillaries by increasing the coagulability of the blood, there is every reason to con- clude that the kidneys are free from organic disease, that life is not in the least endangered. Instances reported in which excellent results have been achieved by the administration of cal- cium chloride in doses of 20 grains three times a day. Calcium lactate in the same dosage is also useful. Both increase the coagulability of the blood. A. E. Wright and G. W. Ross (Lancet, Oct. 21, 1905). Very small proportions of albumin should not be taken into account in relation to life insurance, and conse- quently the writer does not regard as of much moment the eflforts to produce more and more delicate tests for albuminuria. The so-called phys- iological slight albuminuria after ex- cessive exertion, sports, etc.. may also be disregarded. The majority of cases of orthostatic albuminuria are also comparatively harmless; it is ex- ceptional for nephritis to develop later in these cases. In examining it is important to note the absence of the higher blood-pressure character- istic of contracted kidney; also that ALBUMINURIA (LEVISON AND ERLANDSEN). 469 the urine is free from albumin during reclining. Fiirbringer (Deut. med. Woch., Nov. 25, 1909). Teissier distinguishes three groups of orthostatic albuminuria : The true or- thostatic albuminuria, where the albu- min appears very soon after assuming the erect posture. It disappears in the recumbent posture. The mixed ortho- static albuminuria, which, more slow in its development (usually not before ten and twelve in the morning), is found in persons with an earlier acute infec- tion and believed to be due to actual organic changes in the kidney. The associated orthostatic albuminuria is also slower in making its appearance after assuming the erect posture and is associated with abnormal conditions of other organs (dilated stomach, ente- roptosis, movable kidney, etc.). Orthostatic albuminuria was noted by the writer in 14.9 per cent, of 1076 school children in Christiana. It was much commoner among the girls than among the boys, the figures be- ing 13.3 per cent, and 3.5 per cent,, respectively. Bugge (Norsk. Mag. f. Laegevid., Ixxiv, No. 12, 1913). In a study of orthostatic albumin- uria among 189 healthy English school boys, the writer found that 7.5 per cent, showed albumin on arising, 7 per cent, after breakfast, 10.7 per cent, after football, and 18 per cent, after a three-mile run. Nicholson (Pract., xciii, p. 113, 1914). Analysis of 14 cases of orthostatic albuminuria, 9 being children at about puberty, 4 young men and 1 woman of ZZ. The writer concludes that it requires no special treatment, but differentiation is extremely im- portant as otherwise unnecessary re- strictions and other measures are imposed for the assumed underlying nephritis. This is particularly disas- trous in these cases because persons with orthostatic albuminuria are usu- ally frail and may be predisposed to tuberculosis; there is also a tendency to oxaluria. The orthostatic albumin- uria disappeared completely or be- came much attenuated when the oxaluria was arrested by giving a level teaspoonful of calcined mag- nesia two or three times a day. With nephritis, the albumin content of the urine shows little change day or night. Scheel (Ugesk. f. Laeger, Mar. 7, 1918). The writer conducted an examina- tion of the urine of 401 boys and 311 girls in the school before and after the gymnastics class and, when al- buminuria was found, the child was ordered to bring morning urine for examination. The children were all of the upper grades in the school. Albuminuria before the gymnastics was evident in 8 per cent, of the boys and 24 per cent, of the girls; after gymnastics, in 14 per cent, of the boys and 33 per cent, of the girls. In both categories the percentages grew higher the older the children; among the girls of the sixth grade and higher grades the proportion was 49 per cent. Fully 90 per cent, were frail children among those with lordotic albuminuria, and 70 per cent, of those with alljuminuria in general; only 10 per cent, of the total were lively healthy children. Hamelberg (Nederl. Tijdsch. V. Geneesk., Mar. 9, 1918). Even when no casts can be found, albuminuria ought never be regarded as absolutely inoffensive. Although a cyclical albuminuria continuing years may be compatible with perfect health, man)'- authors (Johnson. Greenfield, Bull, etc.) are of the opinion that it sig- nifies the first stage of the evolution of granular atrophy of the kidneys. On the other hand, casts may be found in normal urine and do not mean nephritis. Tuttle, for example, believes that ne- phritis may exist without albuminuria. The writer examined post mortem the kidneys of a youth of 16 who had had typical orthostatic albuminuria during the last 5 or 6 years, but who had been otherwise in normal health 470 ALBUMINURIA (LEVISON AND ERLANDSEN). until he contracted "galloping tuber- culosis" of the lungs. Not a trace of inflammation could be discovered in the kidneys. He reports also 10 clinical cases in which orthostatic al- buminuria was a chronic condition, but in which no tubular casts were ever found. On the whole, vehile al- buminuria may coincide with tuber- culosis, orthostatic albuminuria can- not be deemed an indication of this condition. Hoist (Norsk. Mag. f. Laegevid., Nov., 1915). The albuminuria often found in par- turient women (Aufrecht saw it in 56 per cent, of all cases) must be regarded as physiological. Albuminuria occurring during labor is a reasonable accompaniment of parturition: the quantity is greater than can be considered normal, and is often the greatest seen in any ex- cept a permanent pathological condi- tion. The condition requires no especial and separate treatment, and cannot be considered a permanent pathological lesion. The albumin- uria of labor is differentiated from the other by the presence of labor and by the fact that it ceases after parturition. The more abundant the albumin, the more gradual is its dis- appearance. The albuminuria of the puerperal period is the continuation of that of labor, and is never a separate condition. The all)uminuria of labor is most pronounced toward the end of parturition, especially in cases of diffi- cult or complicated labor. Circum- stances which do not tend to make par- turition especially difficult have no in- fluence upon its albuminuria. The sedi- ment of urine taken during labor shows organized material, including cylin- droids, so often seen in cases of abun- dant albuminuria. These cylindroids are not abundant, and are to be dis- tinguished from others by the fact that they contain superficial kidney epithe- lium in abundance, but not the elements which come from the deeper kidney structures. Jageroos (Archiv f. Gyn., Bd. xci, Hft. 1, 1910; Amer. Jour. Med. Sci., Nov., 1910). In an exhaustive study of several patients the writers noted that the condition appeared in the strong and well-developed as well as in the weak and anemic types. They are inclined to believe that the explanation is to be found in a mechanical cause, re- sulting in congestion of the renal vessels, together with a local and general predisposition. Supporting apparatus l)y improving the posture, gave good results. Fischl and Pop- per (Boston Med. and Surg. Jour., May 4, 1916). PATHOLOGICAL ALBUMINU- RIA. — Pathological albuminuria is found in pathological changes of the blood — as anetnia, leukemia, pseudo- leukemia, scurvy, icterus, and diabetes — even when the kidneys do not present l)athological changes. It is also found in many disorders of the nervous system, as epilepsy, migraine, psychosis apoplexy, neuras- thenia, and Basedow's disease, etc. Delirium tremens has also been men- tioned as a nervous disease often com- plicated with albuminuria. H. H. Schroeder regards excessive eating, overindulgence in alcoholic drinks and possibly tobacco as the most frequent causes of albuminuria. Although the kidneys are theoretically believed to be healthy in the diseases mentioned above, there is no doubt that albimiinuria, in many cases of this class, is Caused by pathological changes of the kidneys. In all febrile and especially in all in- fectious diseases albuminuria is a very frequent .symptom. It has been noticed in enteric fever, diphtheria, variola, after vaccination, in erysipelas, influ- enza, rheumatic fever, pneumonia, etc. In these cases the albuminuria is caused by changes in the coiuposition of the blood, increase of blood-pressure, rise of temperature, and finally by changes ALBUMINURIA (LEVISOX AND ERLAXDSEN). 471 in the structure of the kidneys, espe- cially of the tubular epithelial cells caused by the toxic substances excreted. The presence of albuminuria in pregnancy, as stated above, is com- mon (56 per cent.). Casts are only found in about 50 per cent, of these cases of simple albuminuria. The so- called kidney of pregnancy is to be regarded as a specific toxic nephritis which tends to recur in subsequent pregnancies. The prognosis of it, if properly treated, is good. Albuminuria has been observed in diseases of the intestines, dilatation of the stomach, ileus, ruptures, etc., and in renal venous congestion caused commonly by disease of the heart or the great vessels. It is present in all diseases of the kidneys. Acute, as well as chronic, albuminuria is generally found in the diffuse forms of nephri- tis, as well as in circumscribed renal diseases — such as infarcts, abscesses, or tumors. After retention of urine the portion of urine first passed is frequently albuminous. Albumin is found in many diseases of the ureter, the bladder, the pros- tate and urethra. Ballinger speaks of prostatic albuminuria as a name for an albuminous secretion from an hyperemic or inflamed prostate. This prostatorrhea is constant in chronic prostatitis and often increases regularly every ten to thirty days. It should not be taken for a true al- buminuria. The writer recognizes the existence of a distinct and well-characterized form of albuminuria of rather favor- able prognosis that is not due to a nephritis of toxic or infectious origin, to circulatory disturbances in the kid- neys, nor to general cardiorenal dis- ease, but to perversion of the gastro- intestinal and hepatic ductions. Crof- tan (Arch, of Diagnosis, Oct., 1908). After a study of 62 cases the writer challenges the prevailing view that while the diseased kidne\' may not permit urea, salt or even water to pass, it will allow the big albumin m.olecule to filter through. His study and e.xperiments showed that inflamed kidney epithelium does not allow the passage of serum albumin, and that the albumin found in the urine does not come from the blood but must be secreted by the renal epithelium itself, an active, vital function. All the tests showed that filtering ascites fluid, pleural effusions, blood serum and similar fluids through a delicate animal membrane, such as the rabbit and cat intestine, the albumin content of the filtrate was about the same as that of the original fluid, and the pro- portion of albumin to globulin per- sisted unmodified, but when the mem- brane was hardened or otherwise ren- dered less permeable, the globulin was arrested first; with increasing imper- meability none of the albumin passed into the filtrate or dialysate. Apply- ing these findings to conditions in the kidney, either the proportion of globulin and albumin should be the same in the urine as in the blood, or the albumin should predominate. But this is not the case with diseased kid- nej-s. A relative excess of globulin was found in the urine in simply con- gested kidneys and in orthostatic albuminuria. Mandelbaum (Deut. Archiv f. klin. Med., Oct. 24, 1920). Merk found that many affections of the skin, eczema, pruritus, urti- caria, erythema, and furunculosis, are intimately associated with albumi- nuria. Gunsberger noted albumi- nuria during a severe attack of acute urticaria. Nicolas and Jambon and Boas hold that albuminuria is a fre- quent accompaniment of scabies, but it is not satsfactorily settled how it produces this phenomenon. Lancereaux observed frequently al- 472 ALBUMINURIA (LEVISON AND ERLANDSEN). buminuria in his cases of gouty, her- petic diabetes, but never noted it in his 40 cases of pancreatic diabetes. Glycosuria alone does not entail al- buminuria. When it occurs it may be connected with arteriosclerosis, with subsequent lesions of the kid- neys and heart, or be due to some intercurrent affection, tuberculosis in particular. Certain remedies may also give rise to albuminuria. The prognosis and treatment of albuminuria, therefore, depend en- tirely on the origin and causes of it, and the reader is referred to the various diseases in which it occurs as a symptom. Investigations showing the existence in many cases of a direct relationship between the acid content of the urine and the amount of albumin and tube casts present. In the first case of al- buminuria, the administration of phos- phoric acid was found to cause an im- mediate increase in the albuminuria. In other words, with an increased acidity of the urine, there was a corre- sponding increase in the amount of al- bumin. On the administration, how- ever, of alkalies in place of the acid, the albumin and tube casts diminished and finally disappeared. All the cases which were examined showed that, with increased acidify, there was increased albuminuria, and, corresponding with a diminution in acid, there is a diminution in the albuminuri \ At the same time, in all cases of advanced grave kidney trouble, and especially in uremic pa- tients, the relationship to acidity cannot always be demonstrated. The writer goes on to show that not only is the alblnninuria lessened by alkali adminis- tration, but the functioning of the kid- ney is greatly improved and the very important excretion of chlorides is ac- celerated. The best mode of adminis- tration of the alkali is in the form of the ordinary sod. bicarb., which must sometimes be given in large doses. V. Hoesslin (Miinch. med. Woch., Aug. 17, 1909). Alljuminuria is most constant after operations on the abdominal, genital and urinary organs. In case of pre- existing kidney lesions rapid operat- ing is necessary. The general anes- thesia kept up for an hour or longer might prove fatal just as well with- out any operation, other things being equal. The writer observed albumin- uria after accidental traumatism, showing that the shock is the main factor rather than the anes- thetic in postoperative albuminuria. Satre (Paris med., May 26, 1917). The writer calls attention to a form of chronic nephritis with albu- minuria which is often insidious and found in apparently healthy persons in the course of routine examinations. The same affection has also been classed among the cyclic or orthos- tatic albuminurias of adolescents. The features are those of a non-pro- gressive nephritis with small amounts of albumin, occasional granular and hyaline casts, and a normal phenol- sulphonephthalein excretion. Such cases usually show no obvious cause of the nephritis and albuminuria, but on careful examination there will be found to be some chronic focus of in- fection, such as the tonsils, kidney stone, etc., removal of which leads in a few months to complete recovery of normal kidney function with free- dom from albumin and casts in the urine. Several illustrative cases are given by the writer. In one of these the infection was bronchial and the staphylococcus was isolated from the sputum. The administration of a vaccine cured both the infection and the nephritis. Dental abscesses are also very frequent foci of infection which lead to these forms of neph- ritis. While recovery follows the re- moval of all foci of chronic infection, its progress may cover several months, during which the irritation of the kidneys is being gradually re- paired. David Riesman (Jour. Amer. Med. Assoc, Dec. 15, 1917). ALBUMINURIA (LEVISON AND ERLANDSEN). 473 TESTS. — By means of the tests commonly employed the presence of albumin in the urine is revealed, but no attempt is made to discern be- tween the different proteids ; the dif- ferential diagnosis between the serum- albumin, globulin, etc., will be given later on. The sample of urine to be examined must be very limpid without deposits of any kind; if this be not the case, the urine should be filtered previous to the examination, because a slight cloud of coagulated albumin will only be discernible when the fluid is very clear before the reagent has been added. When the urine contains many bacteria, even repeated filtra- tion will be insufficient to make it clear; this can then be done, however, by addition of a solution of sulphate of magnesia and of carbonate of soda. By shaking the mixture a precipitate of carbonate of magnesia is formed, and when this is removed by filtra- tion the filtrate will be perfectly clear. In many cases a few drops of caustic soda will clear the urine, but urine treated in this manner will not give a precipitate of albumin by boil- ing, while the test of Heller is practi- cable also in this case. Test by Boiling. — A few c.c. of urine are heated to the boiling point and some (5 to lOj drops of nitric acid added. When the urine is acid the albumin will ordinarily coagulate by boiling alone and precipitate as a whitish powder or in small flakes. The nitric acid is nevertheless in all cases to be added, as well in order to complete the precipitation of albu- min as to avoid mistakes caused by the presence of a precipitate of phos- phates or carbonates, — which will immediately dissolve when nitric acid is added. This test is very delicate and will reveal 0.01 to 0.005 per cent, of albumin. Instead of nitric acid, acetic acid can be employed, but, while the nitric acid is to be added after boiling and in a quan- tity of 5 to 10 drops, acetic acid is added before the boiling, and only a sufficient quantity (1 to 2 drops) should be employed as to make the urine but slightly acid. This is espe- cially necessary when the urine is alkaline, because the alkaline albumi- nates with a surplus of acetic acid give a compound which is not coagu- lated by boiling. Tretrop heats the urine nearly to a boiling point and adds a few drops of a 40 per cent, solution of formalin. The albumin coagulates like white of egg. After pouring off the fluid, the proportion of albumin can be deter- mined by weighing the coagulum left. Bychowski describes the following simple method to detect the presence of albumin, even if only a few drops of urine can be obtained : One or 2 drops of urine are put in a test-tube of hot water. After shaking, a whitish cloud is formed, if albumin is present. The test is very distinctive and is still more apparent when the test-tube is held against a black back- ground. Of course, phosphates give the same reaction, but the cloud dis- appears on the addition of a drop of acetic acid. Test for albumin in the urine in which the extra work of having a con- trol or the filtering of the urine or the modification of its reaction has been eliminated. Material needed for the test : Satu- rated salt solution, acetic acid, test- tube, pipette. On heating urine three substances may be thrown down : albumin, nucleo- 474 ALBUMINURIA (LEVISON AND ERLANDSEN). proteid, and phosphates. About 5 to 10 c.c. of saturated salt solution, slightly acidulated with acetic acid, is heated to boiling in a test-tube. The urine to be tested is carefully allowed to run on top of the hot salt solution by means of the pipette. In order to make a good picture, the quantity of urine used ought to equal that of the salt solution. By means of the heat in the sat- urated acidulated salt solution the above-mentioned substances are likely to be precipitated, but, owing to the contact, the saturated salt will not let the nucleoproteids appear, while the phosphates are also held in sus- pension by the acid ; hence nothing can appear at the point of contact of the hot saturated salt with the urine except albumin. Depending on the quantity of albumin present the reaction will be marked or only a film will appear overlying the clear, crystal-like salt solution. It is in urine with a trace of albumin in which this test shows extreme delicacy. The clear, crystal-like salt solution and the control-column of urine above with the surface of contact contrast quite decisively in distinguishing a delicate cloud. Different pictures are produced in the great variety of urines by means of this technique : — 1. In clear urine which contains no albumin the delicate point of contact where the urine rides the hot salt solu- tion is better brought out by setting the solution in motion by gently shak- ing the tube to and fro. 2. In clear urine sometimes a cloud appears some distance above the point of contact. This is due to the heat, which, traveling farther and faster than the acid of the salt solution, throws down a phosphate cloud. 3. Cloudy urine due to phosphates or urates is cleared at the point of contact because the acid and the heat dissolve these, respectively. 4. In cloudy urine due to bacteria no change is seen in the urine at the point of contact, and here, at times, only a close scrutiny of the urine above the crystal-like salt solution below in com- parison with the zone of contact will give us the correct reading. 5. In urine containing albumin clouded by urates or phosphates, the albumin cloud at the contact differs in density from the remainder of the urine. Often the film of coagulated albumin is so delicate that the clearing of urates or phosphates is again seen above that of the contact zone. 6. In albuminous urine clouded by bacteria the coagulated albumin at the point of contact accentuates its pres- ence by its difference in density. It is in cloudy urine that the control of a clear, crystal-like liquid below the urine above emphasizes the beauty of the reaction in the zone of contact. This test is a modification of the saturated salt, or brine, test, yet it adds to this old method the new qualities of diminished labor, simplicity, and ac- curacy. H. L. Ulrich (Jour. Minn. State Med. Assoc, Feb. 15, 1909). Method of employing the acetic acid test for the detection of albumin which has long been used in France: 20 c.c. of urine, about three-fourths of a test-tube 1.5 cm. in diameter, are treated with 5 drops of 20 per cent, acetic acid, mixed, and one-half poured into a second test-tube. The contents of one tube are boiled, the other serving as a control. Albumin produces a cloud or precipitate in the boiled tube. Before testing, the urine must, of course, be perfectly clear; if necessary, it is shaken with Kieselguhr and filtered. If the acetic acid causes a cloud in the cold (nucleoalbumin"), it is cleared by filtration before boiling. An alkaline urine should be acidulated slightly to prevent the precipitation of the phos- phates, or, if a precipitate of phos- phates appears when the urine has been treated with acetic acid and boiled, a few more drops of the dilute (20 per cent.) acid may be added to dissolve it. This will not redissolve even a slight albuminous cloud, pro- vided the urine is not boiled again. Glaesgen (Miinch. med. Woch., Bd. Iviii, S. 1123, 1911). ALBUMINURIA (LEVISON AND ERLANDSEN). 475 Heller's Test. — Three to 4 c.c. of nitric acid are poured in a test-tube and a few c.c. of urine are cautiously filtered down along the sides of tlie tube without shaking the latter. The nitric acid rests on the bottom of the test-tube, and where the fluids are in contact a distinctly limited disk of grayish-white precipitate will appear. When only traces of albumin are pres- ent the precipitate will only take place after some minutes. The more or less distinct violet coloring which also ap- pears at the point of contact of the two fluids is due to oxidation of indican or other chromogens. This test is very delicate and reliable; 0.003 per cent, of albumin is revealed by it. Fallacies, — By the addition of nitric acid the urates or urea are also pre- cipitated; these will not form a limited disk, but render the urine turbid. Resinous acids (copaiba, etc.) are precipitated by nitric acid, but are dissolved by the addition of concentrated alcohol. This error can be avoided by diluting the urine or by moderately warming the nitric acid before the test. Very often also a fine disk or ring will appear above the point of contact. This precipita- tion is due (Morner) to the presence of nucleoalbumins (mucin, chondrolin, sulphuric acid, etc.) and is more dis- tinct after dilating the urine. Test by Acetic Acid and Potassic Ferrocyanide. — The urine is rendered acid by acetic acid, and some drops of a solution of potassic ferrocyanide are added. This reagent, the serum-albu- min, the globulin, and the albumoses are precipitated, while none of the normal constituents of the urine are (Huppert). Heynsius's Test. — A still more deli- cate test than Heller's is that of Heyn- sius, by acetic acid and sulphate of soda. The urine is rendered acid by acetic acid, and an equal volume of a saturated solution of sulphate of soda (or of common salt) is added. The mixture is boiled, and all kinds of albumin will then be precipitated in white flakes. The Magnesium-nitric Test (Rob- erts's).— One c.c. of nitric acid is mixed with 5 c.c. of a saturated solu- tion of sulphate of magnesium, and a small quantity of this mixture is added to the urine. The albumin will be precipitated as a distinct ring. Metaphosphoric Acid (Hinden- lang's) also precipitates albumin in the same manner as nitric acid ; but this test is not as delicate as that of Heller. The solution of metaphosphoric acid must be freshly prepared for use, as the solution easily changes to orthophos- phoric acid upon standing, which does not precipitate albumin. Picric Acid Test (Johnson's). — A few drops of a saturated solution of picric acid will cause a white precipitate when albumin is present ; this test is only indicative of the presence of albu- min, however, when the precipitate appears immediately. The urine must be acid. After some time the uric acid and the creatinine will also be pre- cipitated (Jaffe). Fallacies. — By addition of picric acid and peptones, the resinous acids, — such as those of copaiba, — and alkaloids — such as morphine — are precipitated. Perchloride-of-mercury or Spiegler Test. — A solution of 8 grams of mer- cury, 4 grams of tartaric acid, 20 grams of glycerin in 200 grams of water pro- duces a precipitate of albumin. The test is carried out in the same manner as Heller's test. It is very delicate (it reveals 0.0002 per cent, of albumin), but is not reliable when the urine is poor in chlorides (Jolles). 476 ALBUMINURIA (LEVISON AND ERLANDSEN). Millon's Test. — A solution of nitrate of mercury is added to the urine and the mixture heated to boiling. Nitrate of potash is then added ; the albumin presents as a precipitate of red flakes. This test is disturbed by the sodium chloride of the urine and will be much better if tried upon the precipitate after boiling the urine. Tanret's Test. — The reagent of Tan- ret is composed of perchloride of mer- cury, 135 grams; iodide of potash, 3.32 grams ; glacial acetic acid, 20 c.c ; dis- tilled water, sufficient to make 100 c.c. Some drops of this mixture are added to the urine, when it will coagulate the albumin. It will also, however, pre- cipitate the urates. Tognetti described a "tannohydro- chloric" test wdiich reveals albumin, even in a proportion of 1 to 2,000,000. An equal amount of 1.5 per cent, alco- holic solution of tannin is added to the urine. After heating, an equal amount of 33 per cent, hydrochloric acid is added. A yellowish-white precipitate is gradually thrown down. Cokjuhoun recommends a solution of carbolic acid in absolute alcohol ; this gives a white, milky precipitation of albumin. The test is said to show 0.002 per cent, albumin. Many other reagents have been recommended, which cannot be men- tioned in detail. The boiling test. Hel- ler's test, the potassic ferrocyanide test, and the picric acid test are the most practicable and quite sufficient in gen- eral work. After illustrating the disadvantages of various procedures hitherto widely recommended, the writer advocates, after extensive clinical experience, a diaphanometric method. In prepar- ing the necessary standard solution, the albumin content of a given albumin- ous urine is first accurately measured by the weighing method. Some of the urine, previously filtered, is then diluted with a solution consisting of sodium chloride, 7.5 grams, and mer- cury cyanide, 1 gram, in distilled water, enough to make 1 liter, until it contains 1 gram of albumin per liter. In successive test tubes of equal diameter are now placed re- spectively, 0.5, 0.7, 0.8, 0.9, 1.0. 1.2, 1.4, 1.6, 1.8, and 2 mils of the result- ing mixture, and the fluid in each tube made up to 10 mils with the chloride cyanide solution. The vari- ous tubes thus correspond to samples of urine containing from 0.05 to 0.8 gram of albumin per liter. To each tul^e is added 2 mils of a 20 per cent, solution of trichloracetic acid. A tur- bidity of increasing intensity in the successive tubes is thus produced. After being shaken, the tubes ate carefully stoppered or sealed and labelled. File marks at 10 and 12 mils are now made on an additional tube of the same diameter as the standard series. In testing urine, a test for gross albumin content is first made by the qualitative method and the urine, if necessary, diluted with saline solution so as to contain from 0.05 to 0.2 gram of albumin per liter. The urine is then placed in the empty tube up to the 10-mil mark, trichloracetic acid solution added up to 12 mils, and the mixture shaken. The standard tubes are now all shaken and the urine mixture under test compared with the standards until an equal degree of turbidity is found. Bauzil (Jour. Amer. Med. .Assoc, from Paris med., Oct. 5, 1918). Xanthoprotein Test. — .Vlbuminous urine heated with a surplus of con- centrated nitric acid will take a yellow color, and some of the albumin coagu- lates in yellow flakes, which are soluble in alkalies with an orange-red color. Very minute quantities of albumin may be detected in the urine by means of the deviation-of-complement test. For antigen the writer has used the serum of rabbits which had been im- munized against human blood-serum. ALBUMINURIA (LEVISON AND ERLANDSEN). 477 When albuminous urines were diluted to such a point that they no longer gave a reaction with heat and acetic acid or with nitric acid, they still yielded positive results by the comple- ment-deviation test, while in many instances albumin could be detected by this method in diluted urine w^hen it could not be demonstrated by the ordi- nary chemical tests. The deviating power of the urine is not affected either by filtration through a Rerkefeld filter or by dialysis. The antibody of the urine was, moreover, found to reside entirely in the serum albumin and serum globulin, and after the removal of the substances from the urine the remaining fluid no longer had the property of an antibody. C. H. Wilson (Jour. Path, and Bact., vol. xiii, p. 484, 1909). Following are two new qualitative tests for albumin in urine, which are apparently specific as well as simple. The first test is with tincture of iodine and sodium bisulphate : A few c.c. (5 to 6) of the urine — which must, of course, be clear — are placed in a test- tube and acidified with a few drops of dilute acetio acid. About Ya volume of tincture of iodine (10 per cent.) is now added, and the whole is well shaken. A dirt}% dark-brown precipitate results. A saturated solution (watery) of sodium bisulphate is next added drop by drop, shaking constantly, until the brownish fluid is decolorized. If the urine contains albumin, one sees a permanent whitish cloud or flocculent precipitate. If no albumin is present, the fluid remains clear after the addi- tion of the sodium bisulphate, and shows only the original urinary color. With minimal quantities of albumin, the reaction becomes more evident on standing a few minutes. The second is with decolorized tincture of iodine : One decolorizes tincture of iodine with saturated watery solution of sodium bisulphate and filters. The filtrate is a clear, rather yellowish fluid, which keeps well. On standing for some time, small, yellow crystals may be precipi- tated, without injury to the reagent. The urine, as in the first test, is acidi- fied with dilute acetic acid. About % volume of the reagent is added and the whole well shaken. If albumin is present, a cloud or a flocculent white precipitate forms, ^\'ith traces of al- bumin the reaction may be delayed a few minutes. Normal urine never shows a cloud with these tests. Oguro (Zeit. f. exper. Path. u. Therap., Bd. vii, S. 349, 1909; Amer. Jour. Med. Sci., Jan., 1910). In certain cases of profound gen- eral intoxication, such as cerebral hemorrhage cases in coma, uremia, and eclampsia, addition of 1 drop of urine to dilute, almost boiling Feh- ling's produces a deep purple color. Blood serum gives the same reaction as do other proteins that are break- ing dow'n to proteoses and peptones, i.e., substances giving the pink biuret test. Nine out of 10 cases seen which gave the test, died. H. Bieler (Jour. Labor. Clin. Med., v, 459, 1920). Transportable Reagents for Albu- min.— Hoffmann and Aazette employ- strips of test-paper previously placed in a solution of the double iodide of potas- sium and mercury until saturated, then removed and dried. Geissler's albumin- test paper is previously placed in a solu- tion of citric acid. The urine which is to be tested should be clear and ren- dered acid by means of a few drops of acetic acid. If there be albumin pres- ent, upon immersion of a slip of paper in the urine a distinct precipitate will appear. Pavy recommends test-pellets con- taining ferrocyanide of soda and picric acid; when albuminous urine is well shaken with a parcel of the pellet, albu- min will be precipitated. Stiitz and Fiirbringer employ capsuloids of gela- tin filled with perchloride of mer- cury, sodium chloride, and citric acid. The relative delicacy of the tests most frequently employed is graphically rep- resented by Unger-\"etlesen, in the 478 ALBUMINURIA (LEVISON AND ERLANDSEN). diagram shown below. The longest columns indicate the most delicate tests. Quantitative Tests. — The only method which gives fully reliable re- sults is the gravimetric method. One hundred c.c. of urine are boiled upon a water-bath half an hour; if precipi- tation does not take place a few drops of a weak solution of acetic acid are added ; the liquid is now brought on a weighed filter and the precipitate Ferrocyanide of potassium and acetic acid Solution of picric acid Test-paper Solution of sulphate of soda and acetic acid Heller's test Picric acid in crystals Magnesium-nitric test (Roberts). Trichloracetic acid Metaphosphoric acid Boiling and nitric acid repeatedly washed with hot water. The filtrate must once more be acidu- lated with acetic acid and boiled agp.in, in order to ascertain whether the precipitation has been quantita- tive. When the water has been removed from the filter by strong alcohol, and the alcohol with pure ether, the filter is dried at a tempera- ture of 110° to 120° C, and the per- centage of albumin determined by "weighing. For clinical use several approxi- mate methods have been invented. Esbach employs an albuminimeter, i.e., a graduated glass tube ; this tube is filled to one mark {U ) with the urine and then to the mark R with the test-solution consisting of picric acid, 10 grams; citric acid, 20 grams ; water, 1 liter. The tube is then closed with a rubber stopper and the contents cautiously mixed (not shaken). The mixture is allowed to stand undisturbed for twenty-four 12 24 ''S 45 60 .7 2 84 96 loS 1: • i ., 1 1 i'- \. ■ '■',' hours and the quantity of precipitated albumin then read oflf. The reading indicates in grams the amount of albumin per liter. The urine must be acid, the specific weight should not be more than 1006 to 1008, and the temperature of the room approxi- mately constant (15° C). Resinous acids must be extracted with ether. The yellow crystals often found on the side of the glass are crystals of uric acid. Christensen recommends another method: the albumin contained in 5 ALBUMINURIA (LEVISON AND ERLANDSEN}. 479 c.c. of urine is precipitated by 10 c.c. of a watery solution of tannic acid (1 per cent.). The albumin having been precipitated, 1 c.c. of an ordinary gum-arabic mucilage is added, the volume brought up to 50 c.c. with water, and the whole con- verted to an emulsion by agitation. Upon a piece of white paper, ruled with black lines 0.5 mm. wide and at equal intervals, is placed a cylin- drical glass measuring 4 cm. in diameter. This is half-filled with water, and as much of the emulsion run in as possible without obscuring the black and white lines beneath the vessel. From the number of cubic centimeters required, reference to a table of calculations arranged by Christensen furnishes the proportion of albumin present in the emulsion. When the urine is alkaline it should be faintly acidified with acetic acid before the precipitation of album.in. This test can be made as well by daylight as by the light of a good lamp, and requires only ten or fifteen minutes; but is not applicable to urine containing a small amount of albumin, the variations amounting to two-thousandths. The polariscope is sometimes em- ployed to estimate the quantity of albumin, but this test is not reliable. It is true that albumin is levorota- tory, but this is also the case with normal urine, and sometimes the color of the urine is too dark to allow the use of the polariscope. Goodman and Stern have pointed out (1908) a quantitative method which gives results in a few minutes. It is based on the precipitation of albumin by phosphotungstic acid in the presence of a mineral acid. One gram of crystallized egg-albumin is dissolved in 100 c.c. of distilled water (solution A) ; 1 c.c. of this solution is diluted with 9 c.c. of distilled water (solution B). Drop in a test-tube 5 c.c. of the following solution : — B Phosphotungstic acid 1.5 Gm. Hydrochl. acid (cone.) 5 c.c. Alcohol (95 per cent.) . .q. s. ad 100 c.c. Now it takes 0.1 cm. (added with a pipette graduated in 0.1 c.c.) of solution B to cause a cloudy pre- cipitate, i.e., 0.0001 Gm. of albumin. The diluted urine is tested in the same manner. For the quantitative determination of albumin in the urine a simple test is recommended by the writer. He uses a round albuminometer. In this he places the urine and the Esbach, reagent and adds thereto 0.1 to 0.2 Gm. of barium sulphate (tungspat); after mixing, the glass is set aside for precipitation. In 4 minutes it is complete. A urine containing over 2 per thousand albumin should be diluted before using the test. Ander- son (Ugeskrift for Laeger, Apr. 26, 1917). By the various tests above mentioned, qualitative as well as quantitative, the dififerent coagulable proteids contained in the urine are precipitated ; it is rarely of any use to dififerentiate them one from another. Globulinuria. — Pure globulinuria without the simultaneous presence of serum-albumin does not occur. In order to precipitate the globulin alone the urine is rendered alkaline with solu- tion of ammonia, after some time filtered, and the filtrate mixed with an equal volume of a saturated solu- tion of sulphate of ammonia. If glob- ulin be present a flaky precipitate will appear. [The same result can be obtained by using a solution of sulphate of magnesia, which does not precipitate the other proteids of urine, or by diluting the urine until it reaches 480 ALBUMINURIA (LEVISOX AND ERLANDSEN). a specific gravity of 1002 and leading a slow- current of carbonic acid through it for two or four hours. After twenty-four to twenty- eight hours the globulin will be precipitated. Levison.] Colorimetric Type. — Autenrieth and Mink (Munch, med. Woch., Oct. 19, 1915) comparing the quantitative findings by colorimetry with other techniques obtained further confirmation of the precision of the colorimeter technique. [A colorimetric method of quantitative albumin estimation suitable for the prac- titioner's use is described by W. Auten- rieth and F. Mink (Miinch. med. Woch., Oct. 19, 1915) as follows: Ten c.c. of clear or filtered urine in a test tul)e are heated for a few minutes on the boiling water l)ath. If a precipitate forms. 2 to 4 drops of dilute acetic acid are added and the tul)e put Ijack in the water bath. Usually at once, but sometimes only after a few minutes, tlie albumin all comes down in large flocculi. If the formation of the fiocculi is difficult because of the urine being poor in salts, 2 to 5 c.c. of saturated sodium chloride solution should be added. The precipitate is then at once placed on moistened filter paper and washed with about 20 c.c. of hot water, the latter hav- ing first been used to rinse out the test tube. The precipitate is next placed in a small funnel over a 10 c.c. graduate. Two to 3 c.c. of 3 per cent, soaium hydroxide solution are placed in the test tube to dis- solve the remaining traces of albumin, and then over the precipitate itself, most of which easily goes into solution. Addi- tional 2 to 3 c.c. portions of the alkali are now used, until the all)umin is completely dissolved and the total amount of solution is about 9.5 c.c. Four or 5 drops of 20 per cent, copper sulphate solution are now added, the graduate filled to the 10-c.c. mark with alkaline solution, and the mix- ture well shaken up for two or three minutes. After allowing it to stand five or ten minutes, a clear supernatant fluid suitable for colorimetric examination will usually be found; if not, the mixture may be filtered through dry filter paper, the first few drops being discarded. The solu- tion having been placed in the glass trough of the Autenrieth-Koenigsberger colorimeter, comparison is made 5 or 6 times with the wedge-shaped color scale of the instrument until 2 or 3 readings correspond. The tuial reading is then re- ferred to a curve chart, which shows the number of milligrams of albumin in the 10 c.c. of urine. The method is held to be very accurate. Where the urine is be- lieved to contain less than 1 gram of albu- min per liter 20 c.c. instead of 10 c.c. of urine shoul . be used, and where it ex- ceeds 4 grams, only 5 c.c. Lewin (Med. Klinik, July 13, 1913) em- phasizes the delicacy and reliability of the color reaction which follows when dis- solved albumin is treated with a mixture of 0.1 to 0.15 parts trioximinomethjden in 1(X) parts crude sulphuric acid. Even a 0.02 per cent, solution of t\i,^ albumin shows the characteristic violet tint. In the colorimetric method of Claudius, of Copenhagen, as described by Kahn and Silberman (N. Y. Med. Jour., Oct. 3. 1914) the urine is first filtered and its reaction tested to see if it is neutral or slightly acid. It is then diluted with an equal por- tion of a 2 per cent, sodium chloride solu- tion. To 5 c.c. of the diluted urine, add now 5 c.c. of Claudius's reagent, which consists of 2 per cent, trichloracetic acid, 0.5 per cent, tannic acid and 0.1 per cent, acid fuchsin. The mixture of urine and reagent is then well shaken in a stoppered 15- or 20- c.c. flask, filtered, and the filtrate compared with a standard in the Sahli or Cowers hemoglobinometer. Norgaard (Ugeskrift for Laeger, No\'. 25, 1915) has been giving Claudius's quan- titative colorimeter test U r albumin a thorough trial in 100 specimens of urine and in some other organic fluids, and found that by comparative tests, with an albumin content below 1 per thousand there may be a ditlerence up to 10 per cent, of the findings on analysis by weight. With an albumin content above 1 per thousand, the difference could rise to 20 or 30 per cent., averaging 2.5 per cent. C. E. DE M. S.] Miscellaneous. — D- iters (Miinch. med. Woch., Dec. 12, 1916) heats an ordinary test tube until the bottom is sufficiently soft to allow its being pushed up into the tube so as to make a small ball-«haped or conical depression in its lower end. In this are poured 6 to 8 drops of nitric acid ALBUMINURIA (LEVISON AND ERLANDSEN). 481 and the urine poured on top. The tur- bidity resuhing is more distinct than is obtained with the old test tube owing to the increase of Hght which passes through the fluid. Benedict (letter to the N. Y. Med. Jour., Nov. 28, 1914) describes the following simple method to estimate the albumin: Boil the urine thoroughly, adding 1 drop of nitric acid. Centrifugate until the pre- cipitate is no longer condensed. The per- centage reading is about 6 times the per- centage by weight of dried albumin. If the moist precipitate is large, say more than 1 c.c. (16 minims) in a 10-c.c. (2% drams) tube, which rarely happens, even when urine is said to coagulate entirely, the lower portion of the precipitate is still further compressed. This method is sim- ple and rapid, and is reasonablj^ accurate, sufficiently so for clinical use. A test described by Osmond (Lancet- clinic, Dec. 13, 1913) is asserted by him to be equal in delicacy to any other, and to have certain features which make it superior to them for routine use. The fol- lowing solution is employed: Picric acid S parts Citric acid 10 parts Sodium chloride 100 parts Distilled water 1000 parts Technique. — Place 2 or 3 c.c. of the re- agent in a test tube. Filter the urine until it is perfectly clear. Then allow urine very gently to float upon the surface of the reagent in the inclined test tube. Al- bumin will show as a white zone at the line of contact of the two amber fluids, which are practically iso-chromic. D. W. Prentiss (Med. Council, Aug., 1912) gives the following method to record the amount of albumin in urine in such a way that it can be compared with later examinations in the same case, or with other cases. The record is permanent, easy to make, and sufficiently accurate to be of the utmost value to the busy physician: 1. Make the underlying nitric test for albumin, in a test tube. 2. Allow the tube to stand 2 min- utes. 3, Hold the tube between a black or dark object and the eyes, on the level with the eyes. 4. Note the exact thickness of the ring of albumin at the line of contact. 5. On the chart draw parallel vertical lines 1- which represent the test tube. Connect these lines by a cross line the exact breadth of the thickness of the coagulated albumin. H. E. Jones (Glasgow Med. Jour., Jan., 1916) reports a case in which results of albumin determination in the urine with the Esbach procedure proved misleading, owing to a high degree of alkalinity of the urine tested. Although an albumin pre- cipitate was obtained in the heat and acid tests, no precipitate was obtained in the albuminometer owing to the fact that the amount of citric acid contained in Esbach's reagent was insufficient to acidulate the urine to the extent required for precipita- tion of albumin by the picric acid in the reagent. In all very alkaline urine this source of possible error in the interpreta- tion of the test should be borne in mind. Lenk (Deut. med. Woch., Oct. 21, 1915) recommends the following rapid test for albumin and sugar. Albumin, enzymes, etc., are absorbed by negative substances like kaolin, charcoal, pulverized pumice stone, etc. If these are mixed with the urine after addition of Esbach's reagent (a mixture of 5 Gm. — 75 grains — picric acid with 10 Gm.— 2i_> drams — citric acid in 500 c.c — 1 pint — water) as the particles settle to the bottom of the dish they carry the albumin down with them. Using pul- verized pumice-stone, the albumin is pre- cipitated completely in 10 minutes. An improved technique for Tsuchiya's phosphotungstic-hydrochloric acid-alcohol reagent for detecting albumin in the urine is offered by Sueyoshi (Mitteil. a. d. med. Fakul. d. k. Univ. Tokyo, xiv. No. 3, 1915). The reagent is a mixture of 20 Gm. mer- curic chlorid; 5 Gm. potassium bromid; 10 c.c. hydrochloric acid (30 per cent.); water 55 c.c. and alcohol (95 per cent.) to 100 c.c. The test tube is filled about half full of urine and about seven-eighths as much of the reagent is poured in and thoroughly mixed with it. The albumin sediment is measured next day as usual. According to the writer, the forma- tion of picric acid crystals in 10 c.c. of urine treated with 5 c.c. of Es- bach's reagent is a delicate test for '■ albumin. A positive response throws light on the prognosis. The crystals are found more numerous as recovery progresses, either in acute or chronic -31 482 ALBUMINURIA (LEVISON AND ERLANDSEN). kidney disease. The changes in the proportion of crystals always foretell the next stage of the disease. Bergell (Zeit. f. klin. Med., xc, No. 5-6, 1921). TREATMENT.— T. C. Janeway (Amer. Jour. Med. Sci., Feb., 1916; N. Y. Med. Jour., Feb. 12, 1916) stated that for the most part treattnent in the past was purely schematic, based on a conventional diagnosis, and usu- ally involved violent interference with the habits of a lifetime. To tell every patient with albuminuria or hypertension to stop eating red meat, or, worse, to go on a diet, is evidence of ignorance. He divided the cases into 5 types. The first type is one in which albu- min and casts in the urine are the only evidence of disease. If the treatment of acute nephritis results in a steady subsidence of albuminuria, it .should be persisted in, just as though the patient had a known acute nephritis, but if a week in bed on a milk diet has no ap- preciable effect on, the albumin and casts, the bed and milk diet are an un- warrantable hardship. In children the question of a postural albuminuria should be cleared up without delay. The eft'ect of exercise and cold baths should be studied carefully, as these may cause an albtmiinuria. Severe physical strain, exposure to cold and wet, and excesses, not only in tobacco and alcohol, but in other things as well, are to be avoided. Soups and spices may wisely be excluded from the diet. Gourmands should have their excessive appetites restrained ; obese patients should be moderately reduced; but if the phthalein test is normal he sees no reason for a restriction of protein, either qualitative or quantitative, below a moderate normal intake. Patients who use much salt should reduce it. The second type is one m which the patients have hypertension with or without a trace of albumin and with slight if any subjective symptoms. The worst advice for a man of important affairs is to give up business com- pletely, but change of occupation may be imperative for the manual laborer. It is of great importance to secure ade- quate normal sleep. A short rest in the middle of the day is of great benefit. Tobacco in excess is a poison. While excessive athletics may be dangerous, exercise is beneficial, and when this cannot be allowed for any reason, mas- sage is helpful. Diet should follow about the same Imes as in the first class, and the use of salt should be moderate. The abuse of fluid is dangerous and a winter vacation in a warm climate is sometimes desirable. The third type is that in which hyper- tension and outspoken myocardial in- sufficiency are present. The heart must be safeguarded by rest in bed or in a chair. Those with auricular fibrillation need digitalis, those without should also receive the drug, but some of them do not respond as well. Toxic effects must be watched for, as some patients with regular rhythm are made worse by •digitalis. Then one of the caffeine diuretics should be tried, theocin, about 12 grains (0.77 Gm.) a day, or diuretin, about -10 grains (2.6 Gm.) in divided doses, not oftener than every other day. The fluid intake and the urine output must be measured accu- rately. Diuresis from digitalis should not be expected within 48 hours, but that from the caffeine group may be ob- served on the day of administration and the next doses should be given when the diuresis ceases. The symptoms tliat demand treatment are dyspnea, edema, and the whole picture of cardiac fail- ALBUMOSURIA. 483 ure with passive congestion of the vis- cera; vasodilators are indicated. He speaks highly of fresh nitroglycerin tablets dissolved on the tongue and not swallowed. Theobromine has been found to give good results in some cases. Regulation of the diet and reduction of fluids and salt are indicated. The fourth type is one of general edema zvitJiout notable myocardial in- sufficiency. These patients excrete small quantities of salt, so treatment should always begin with a period of very low salt and water intake to pro- mote rapid absorption of the dropsy. Bed is desirable until normal function is restored, and if the dropsy disappears the further treatment is that of con- valescence from acute nephritis. Ob- stinate edema requires other dehydrat- ing measures, sweat baths, hot packs, perhaps purging. The fiftit type is that of advanced renal insufficiency. Treatment is purely symptomatic. Paroxysms of dyspnea and of Cheyne-Stokes breathing de- mand special relief. Morphine is effective in many cases, but may in- duce anuria with coma. Chloral hy- drate in 5- or 10- grain (0.3 to 0.6 Gm.) doses, alone or with bromides, sometimes is effective. The patients should be encouraged to sleep in a chair instead of insisting that they go to bed. Diet should be reduced to a minimum by the patient himself. Bleeding has its greatest value in sudden convul- sions, when the removal of 500 or 600 c.c. of blood is indicated. Sweating occasionally is of benefit. F. Levison AND A. Erlandsen, Copenhagen. ALBUMOSURIA. — Albumose oc- curs in the urine under various circum- stances. It may appear when large quan- tities of pus, such as in empyema, a large abscess, etc., accumulate in any. region; in chronic suppurative processes, intestinal, peritoneal, meningeal, etc.; in pyogenic nephritis, and when there is a consider- able destruction of white corpuscles. It ma\' also indicate a more or less rapid tissue disintegration, caused by patho- genic organisms, as in pneumonia, particu- larlj' in the resolution s'tage; hepatic dis- orders, especially acute yellow atrophy. This form is usually temporary. The writer has encountered albu- mosuria in five pregnant women. It always disappeared a few days after deliver}- and did not seein to have any pathologic or prognostic import. Tanberg (Norsk Mag. f. Laegevidens- kaben, Jan., 1918). Case in a woman of 39 years, the outstanding points of which were the presence of the albumose in the urine, with a relative and total in- crease of small lymphocytes in the blood, and the absence of an}' signs of malignant growths, and cardiac enlargement, with murmur, and dropsy in the legs, together with the presence of streptococci in the urine. Heimann and Wilson (Lancet, Dec. 28, 1919). In a rare form known as "iiiyelopatliic albumosuria or Kaliler's disease," character- ized by a copious excretion of Bence- Jones proteose, the latter is persistent, and is usually associated with sarcoma- tous degeneration of the bone marrow. This form runs a rapid course and is in- variably fatal. A. Graham-Stewart (Clinv ical Jour., Mar. 29, 1916) observed 3 cases of albumosuria in children due to intes- tinal toxemia, witli mucous colitis in one of the patients. Toxemia of intestinal origin is regarded by the author as an un- recognized cause of albumosuria. He urges the importance of an earh* dis- tinction between the latter and albumin- uria. Heller's test for albumin then gives a bulky precipitate. This does not form with nitric acid so definite a ring as does albumin. It is more woolly and tends to 484 ALCOHOL (SAJOUS). float to the top. It may at once be dis- tinguished from albumin by heating when the ring or cloud disappears to reappear on cooling. Again the ordinary heat test does not cause albumose to form a cloud. Martindale gives the following tests for the detection of albumoses: Acidulate the specimen with acetic acid, and add 10 per cent, potassium ferrocyanide solution. This precipitates pri ary albumoses. This ferrocyanide precipitation distinguishes albumose from compound protein. On warming, the precipitate dissolves, to re- appear on cooling. This distinguishes it from that due to serum albumin. Again, alter precipitation by salicylsul- phonic acid, albumoses dissolve on heat- ing and reappear on cooling. There is also the Biuret reaction. Albu- min is tested for by Heller's test; if pres- ent, it is removed Ijy 10 per cent, trichlor- acetic acid solution and the Biuret test applied to the filtrate. To do this, 1 drop of a 2 per cent, copper sulphate solution is placed in a test tube; 5 c.c. of the urine are added, and then 5 c.c. of a 10 per cent, solution of sodium hydroxide. The pres- ence of albumose is indicated by a rose pink. As regards the Bencc-Jones form, Mar- tindale states that this albumose is de- tected by: Coagulating at 58° C, J.^., lower tlian serum albumin, which coagu- lates at 75° C. ; precipitates with hydro- chloric acid; precipitates with nitric acid in the cold; on raising to the boiling- point, however, the coagulum dissolves more or less completely, and reappears on cooling; precipitates with potassium fer- rocyanide and citric acid (often takes time to develop, differing in this respect from all)umin). The hj'pochloric acid test is stated to be very sensitive, and not to depend on ex- cess of salts. The result is obtainable after very free dilution of the specimen. S. ALCOHOL.-Alcohol is one of a group of hydrocarbon compounds which have as their base a radical desig- nated as ethyl, chemically represented by the formula C2H5. Alcohol is a hy- drate or hydroxide of ethyl — C2H5OH. To distinguish it from other more toxic members of the series of alcohols, par- ticularly fusel oil (chiefly amyl alcohol) and wood spirit (methyl alcohol), the spirit used in medicine is called ethyl alcohol. It is obtained by distillation and subsequent purification from a fer- mented mash of potatoes or grain, from fermented sugar, or from wine, and is known in the British Pharmacopeia as rectified spirit. Absolute alcohol, i.e., alcohol at least 99 per cent, pure, occurs as a volatile, inflammable, colorless liquid, with a characteristic pungent odor and burn- ing taste. Its boiling point is 172° F. {77.7° C). It has a marked affinity for water, which it abstracts from whatever substances it may be in contact with, including the air and the human tissues. It is miscible in all proportions with water, glycerin, ether and chloroform. When absolute alcohol is mixed with water the resulting volume of fluid is slightly less than the sum of the two components before their admixture. Alcohol is a solvent for resins, volatile oils, fats, and alkaloids, and is very extensively employed as such in ])rei)arations containing remedies uf these classes, most of which are insoluble in water. It forms the mens- truum in the ofificial tinctures, spirits, elixirs, and all but two of the fluid- extracts. PREPARATIONS AND DOSE. Alcohol contains 94.9 per cent, by volume (92.3 per cent, by weight of pure ethyl alcohol to 5.1 per cent, of water). Specific gravity, 0.816. Rarely used internally in doses of 1 to 4 drams, diluted with water. Alcohol Dehydratum (Absolute Al- cohol) contains not more than 1 per cent, of weight of water. Specific gravity. 0.797. ALCOHOL (SAJOUS). 485 Alcohol Dilutum (Diluted Alco- can be destroyed in or eliminated from hoi). — A mixture of alcohol and dis- the organism in the interval between tilled water, containing 48.9 per cent, by successive doses. According to Bartho- volume (about 41.5 percent, by weight) low, the quantity which a healthy adult of pure ethyl alcohol to 51.1 per cent, of is able to oxidize in twenty-four hours water. Specific gravity about 0.937. is from 1 to 1}4 ounces of absolute al- Spiritus Frumenti (Whisky), U. cohol. Where this is exceeded, an accu- S. P. VIII. — 14 to 55 per cent, by mulatiou of the drug in the system is volume of absolute alcohol. likely to occur, and the following symp- Spiritus Vini Gallici (Brandy), U. toms may be expected to appear. Flush- S. P. VIII. — 46 to 55 per cent by vol- ing of the face, dryness of the skin and ume of absolute alcohol. mucous membranes, bounding pulse, and Vinum Album (White Wine), U. the odor of alcohol on the breath. Such S. P. VIII. — 8.5 to 15 per cent, by signs indicate, in any given case, that volume of absolute alcohol. the useful amount of alcohol, whether Vinum Rubrum (Red Wine), U. employed for general or merely for di- S. P. VIII. — 8.5 to 15 per cent, by gestive stimulation, is being exceeded, volume of absolute alcohol. In persons habitually taking alcoholic Whisky is produced by the distillation beverages the ability to oxidize alcohol of fermented grain (rye, corn, or bar- is augmented, finding its expression in ley), and brandy by the distillation of increased tolerance ; hence in these indi- fermented grapes. Inasmuch as the viduals, if alcohol is given for the pur- toxic am3dic alcohol is likely to be pres- pose of obtaining therapeutic efifects, ent in freshly distilled spirits, the Phar- the dose will have to be increased, and macopeia specifies that these products even, in many cases, doubled or tripled, shall have been kept in storage for a In febrile states large amounts have certain period before use (whisky, two often been administered without caus- years ; brandy, four years), the amylic ing signs of intoxication, the oxidizing alcohol becoming oxidized into harmless power evidently being heightened dur- ethers. White wine results from the ing the febrile process ; notwithstanding fermentation of the juice of fresh this fact, it is now generally considered grapes, from wdiich the skins, seeds and that small doses of alcohol — if, indeed, stems have been removed, while red it be used at all in these cases other than wine is produced from purple-colored during periods of dangerous circulatory grapes with the skins included. The depression — will give as good results as latter contains more tannin, but less tar- large amounts, taric acid than white wine. In children, as well as in the aged. Dose. — The ordinary dosage of alcohol is well borne. To the former it whisky or brandy in adults imaccus- can be administered in doses proportion- tomed to their use may be said to range ally larger than are suitable for adults, from 1 dram (4 c.c.) to 2 ounces (60 while in the latter the dose need not be c.c). In regulating the dose the capac- reduced from that given to the middle- ity of the individual to oxidize the alco- aged. hoi is to be taken into account, the object MODES OF ADMINISTRATION. being, if alcohol is to be given repeat- — Alcohol, as used in therapeutics, is edly, to limit the amount to that which usually exhibited in dilute form in one 486 ALCOHOL (SAJOUS). of the various spirituous beverages, to arrest of the process of fermentation none of which is now official. They while still incomplete. Sherry ("vinum may conveniently be grouped according Xerici") is a white wine, containing 15 to the percentage of alcohol contained. to 18 per cent, of alcohol. Port and The so-called "spirits" include whisky, sherry of American production are usu- brandy, gin, rum, and arrack, and all ally lighter, the percentages ranging contain about 50 per cent, of alcohol. A from 10 to 18. Madeira is a dark-col- liquor having this percentage is said to ored white wine with 18 to 22 per cent, be "proof spirit," implying that it con- of alcohol. Marsala is a wine similar tains just sufficient alcohol to be infiam- to Madeira, but of Sicilian production, mable. Gin ("spiritus Genevse") is Malaga is a sweet wine, having 17 per made by adding oil of juniper berries to cent, of alcohol. The heavy wines are, rectified alcohol or whisky. The offi- in general, too sweet for the use of sick cial spiritus jiiniperi compositus, with 4 persons; when obtained "dry" (free, or per cent, of juniper oil as well as other nearly free, from sugar), however, they flavoring substances, is a preparation are frequently of benefit to convales- similar to gin, but is stronger in alcohol, cents and to the debilitated, containing 70 per cent.; the average The light wines contain from 5 to 15 dose is 2 drams. Rum ("spiritus Jamai- per cent, of alcohol. Ordinary claret censis") is obtained by distilling fer- ranges from 6 to 12 per cent. This mented molasses or sugar. Like gin, it group also includes Burgundy, the Rhine is not official. Arrack results from the wines, Moselle, Tokay, champagne, and distillation of fermented rice. Spirits hock, in all of which the percentage of contain a large number of other volatile alcohol is usually between 9 and 14. bodies besides the main component, Champagne, though it contains only ethyl alcohol. These include higher about 10 per cent, of alcohol, has a pro- members of the same group of alco- nounced stimulating effect on the gastric hols as ethyl alcohol, as well as alco- mucous membrane because of the large hols of other series and a group of amount of carbon dioxide it liberates, bodies the composition of which re- Wines are more slowly absorbed than mains obscure, known as the renanthic alcohol, and the physiological effects of ethers, and which, though present in the alcohol they contain are correspond- small amounts, give to the various ingly less marked. In addition, wines liquors their characteristic flavors. Spir- possess distinct nutritive value, by vir- its differ radically from wines in that tue of the numerous substances, both they are free of non-volatile compounds, organic and mineral, which they em- which are left behind in the process of body. These include, according to an distillation. analysis of red wine by Gautier, albu- The heavy wines contain about 20 per minoid, fatty, and carbohydrate constit- cent. of alcohol, being made from grapes uents, glycerin, potassium tartrate, suc- having a large proportion of sugar, cinic acid, acetic, citric, malic and They include port, sherry, Madeira, carbonic acids, and salts such as the Marsala, Malaga, and others. Port chlorides, bromides, iodides, fluorides, (formerly official as "vinum portense") and phosphates of potassium, sodium, is a sweet, red wine, containing 15 to 22 calcium and magnesium oxide of iron, per cent, of alcohol ; its sweetness is due etc. Wine also contains a number of ALCOHOL (SAJOUS). 48; volatile bodies, such as are present in brandy in larger amount. Light wines are useful wherever prostration is or has been a marked feature of the case, e.g.. in typhus, intermittent fever, scurvy, and cholera among the more acute diseases ; also in many chronic af- fections, excluding, however, cases of Bright's disease, chronic digestive dis- orders, neurasthenia, anemia, and dia- betes. Wines are peculiarly liable to undergo acetic fermentation in the stomach (Hayem), and hence are not well borne in certain gastric dis- turbances. It has been found in I'itro that wines uniformly interfere with peptic digestion. Red wines very usually disagree where there is gastric hyperacidity. In these cases white wines are generally service- able. White wines have a diuretic ef- fect beyond that possessed by the red wines. When very acid, however, they are in themselves capable of causing gastric disorders, and should be avoided wherever diarrhea exists. Many of the Rhine wines are not suited to those having a tendency to the formation of oxalic deposits, owing to the oxalic acid which they contain. Malt liquors (beer, ale, brown stout, porter) contain less alcohol but have greater nutritive value than any other of the alcoholic beverages. They are produced by causing an extract of malt (sprouted barley grains) and hops to undergo fermentation by the yeast- plant. The malt is previously allowed to germinate, in order that the starch it contains shall be transformed into the more easily fermentable sugar. The ' diastase which effects this conversion is formed by the grain itself during germi- nation. The yeast then ferments the sugar with the production of alcohol. The final product contains about 3 to 7 per cent, of alcohol and a large percent- age of solid constituents available for nutrition, including mainly dextrin, sugar; albuminoid, fattj' and gummy substances ; succinic, lactic and acetic acids ; aromatic and bitter principles derived from the hops, carbon dioxide to the extent of 6 to 8 times the volume of the liquor, and a number of salts re- sembling those found in the ashes of meat extract, principally phosphates and salts of potassium and calcium (Man- quat). Beers also contain diastase, which aids in the digestion of carbohy- drate foods and tends to produce obesity. Ale differs from beer in that its fermentation is carried on at a high temperature instead of a low one; it usually has a higher percentage of alcohol, ranging from 4 to 8 or 9 per cent., while beer has 2 to 6 per cent. (4 per cent, on the average). Porter and brown stout are fermented at a still higher temperature ; some of the sugar is converted to caramel, giving these beverages their darker color. They contain 4 to 6 per cent, of alcohol. \\'hen the digestive powers are but little impaired, beer is valuable as a tonic and nutritive. The hops and the carbon dioxide probably both stimulate functionally the gastric mucosa. Where the digestion is weak, the large dextrin and sugar content of beer may undergo fermentation in the stomach. The ab- sorption of beer is. in any case, slower than that of other liquors. Beer diluted with water is said to be better borne than wines where there is hyperchlor- hydria. The low percentage of alcohol contained in beer renders it useful where the patient appears specially sensitive to the action of alcohol on the cerebrum. A syrupy extract of malt is official in the United States Pharma- copeia as cxtr actum malti; it contains 488 ALCOHOL CSAJOUS). large proportions of dextrin, sugar, phosphates and nitrogenous bodies, and but 2 per cent, of alcohol. Less important medically are the wines of other fruits than the grape, and the liqueurs. Among the former may be mentioned cider, which results from the fermentation of apples and contains 2 to 5 per cent, of alcohol, and perry, a similar product made from pears. Cider is useful where diuretic and slightly laxative effects are desired. Liqueurs comprise a large class of alcoholic products differing widely in composition. They are generally made by the addition of essential oils; they frequently contain a large amount of sugar, and are of but little value in therapeutics. In acute diseases alcohol is usually given internally in the form of whisky or brandy. Under the Revenue Act of October 3, 1917, which went into effect December 1, 1917, every physician who wishes to buy alcohol U. S. 1'. for his own use must get a permit from the U. S. Internal Revenue Office, file a bond and state in his appli- cation blank for what purpose he intends to use the alcohol. This applies whether it is for washing his hands or for prepar- ing stains for laboratory use, or for any other purpose for which he desires to use grain alcohol without having it medicated or in some manner denatured. A physi- cian cannot purchase more than one pint of alcohol that has been medicated with- out obtaining a permit. Editors. CONTRAINDICATIONS.— Al- cohol is contraindicated in nephritis and inflammatory conditions of the urinary passages, in conditions associated with marked gastric or intestinal irritation, and in persons likely to acquire the alcoholic habit, — especially young adult or middle-aged neurotics, and persons who have been subjected to traumatism of nervous structures. In prolonged cardiac depression alcohol is likely to do more harm than good. Sweet wines and beer are contraindicated in diabetes mellitus and in eczema. In the diar- rheas of children alcohol should not be administered unless the stomach and bowels have already been freed from putrefying material. Syphilis is always badly affected by alcohol, and the latter is responsible for many of the evil results often seen in this disease, both in the skin and in the nervous system. The syphilitic should be an abstainer from alcohol from the moment of his infec- tion. L. Duncan Bulkley (Med. Rec, Jan. 29. 1910). PHYSIOLOGICAL ACTION.— The effects of alcohol, when it is taken internally, vary according to the size of the dose. The action here to be de- scribed is that of therapeutic or some- what larger doses. Digestive Tract. — In the mouth and pharynx, alcohol ha.s a slightly astringent action upon the mucous membranes. For a brief period it also causes an increased flow of saliva, and when in no greater concentration than 5 per cent., has been found by Storck to favor the digestion of starchy foods by ptyalin. The action of ptyalin is, on the contrary, unfavorably influenced by alcohol in 10 per cent, strength and, more particularly, by the acids con- tained in malt beverages and wines. ( )n reaching the stomach, alcohol proikices a sense of warmth, which is jiromptly followed, as absorption takes place, by a general feeling of well-being and restfulness. When present in the stomach in small amount only, alcohol has no marked effect on peptic diges- tion, and often distinctly augments the secretion of gastric juice, itself becom- ing thereby progressively more dilute. It acts both by stimulating directly the ALCOHOL (SAJOUS). 489 gastric circulation and the secreting cells to greater activity, and probably also by a special secretory influence of the alcohol after its absorption. Since Spiro, Frouin and Moulinier observed that alcohol administered per rectum caused in the stomach a marked flow of abnormally acid gastric juice. Chitten- den and Mendel showed, moreover, that the relative amounts of pepsin and hydrochloric acid in the gastric juice were both increased. Thus alcohol in small quantities tends to hasten gastric digestion. Fatty substances being dis- solved by it, their absorption is facili- tated. The appetite, when poor, is improved. When 5 to 10 per cent, of alcohol is present, peptic digestion takes place less rapidh' than normal, the degree of interference varying with the kind of food to be acted upon. According to Klemperer and Battelli, however, gastric motility is hastened by moderate amounts of alcohol, while Bandl, Scan- zoni and others have shown that liquids containing alcohol are much more rapidly absorbed from the stomach than liquids free of it. It thus happens in many cases that the interference of the alcohol with peptic digestion is more than counterbalanced by the hastened absorption as well as by the increased amount of gastric juice. Gluzinsky's experiments intlicate that alcohol slows gastric digestion only during the period before its absorption ; it then causes in- creased rapidity of digestion because of the special stimulating effect on secret- ing structures already mentioned. Ac- cording to this author 60 Gm. (about 2 fluidounces) of cognac, taken during or before a meal, slows the digestion of carbohydrates and hastens that of meats, but when taken after the meal hinders both. It has been noticed that spirits are much less potent in hamper- ing peptic activity than are wines and especially malt liquors. In small quan- tities they distinctly aid digestion. Using the method first devised by- Cannon, the writer studied experi- mentally the effect of alcohol on the rate of discharge from the stomach in the Laboratory of Physiology in the Harvard Medical School. A rela- tively small amount of alcohol mixed with the food administered to the animals had distinctly an accelerat- ing effect on the rate of gastric dis- charge and produced a higher maxi- mum than the normal. The gastric peristaltic waves were deep and vigorous, and in most cases at the end of 3 hours no residue remained in the stomach. Contrary to these results in the third set of experi- ments where the 95 per cent, alcohol was used there was a slow initial dis- charge and a gradual rise to a maxi- mum at the end of 3 or 4 hours. When at all evident the peristaltic waves were shallow and feelde and in some of the animals there was present at the end of 4 hours a con- siderable amount of food. L. T. Wright (Boston Med. and Surg. Jour., Nov. 2, 1916). Alcohol passes quickly from the stomach into the intestines. Here also it is absorbed, and exerts, when in small amount, an effect similar to that produced on the stomach, viz., stimu- lates the mucous and other glands to increased activity. Relaxation of the bowels and meteorism are frequently influenced by it. In vitro alcohol in 3 per cent, strength, however, slows the digestion of proteids by the pancreatic juice (Chittenden and Mendel). Nervous System. — When the ac- tion of alcohol has been exerted long enough, it acts as a depressant to the nervous system. The effects seen at first suggest primary cerebral stimula- tion, but it is a question whether these 490 ALCOHOL (SAJOUS). phenomena are not really the result of impaired inhibition, in which case alco- hol might be said to act as a depressant from the beginning. Small amounts of alcohol do, indeed, produce efifects sug- gesting loss of inhibitory control over cerebral activities, though it must be admitted that the actual physiological existence of such a controlling function has not yet been definitely proved. In the primary stage of apparent excita- tion, the subject exhibits loss of con- trol, as manifested by loose speech, laughter upon slight provocation, out- bursts of the passions and exaggerated movements. The subject becomes self- ish, irresponsible, and lacks will-power. Bunge, Schmiedeberg and others be- lieve that these phenomena occur be- cause the normal inhibitory influence on the cortical centers has been reduced. Alcoholism may be assumed, the writer concludes, when besides the lesions of chromatolysis in the third layer of large pj'ramidal cells of the brain, there is dilatation or conges- tion of the capillaries, thickening of the meninges, without leucocyte in- filtration, and small hemorrhages. Jones (Prensa Med. Argentina, Sept. 30, 1918). As an argimient against the theory of primary stimulation it is pointed out that a primary stage of excitement is usually not seen when the subject re- mains in quiet and dark surroundings after taking alcohol, while certain indi- viduals show no evidences of stimula- tion under any circumstances, but soon pass into a state of cerebral depression. Other observers believe that the physi- cal excitement and the unusual flow of ideas and powers of speech often ob- served under the influence of alcohol indicate a primary stimulating effect on the same centers. The ability to per- form muscular work has usually been found in experiments to be increased for a brief period by alcohol in small amounts, especially where fatigue ex- ists, but this is very promptly followed by a distinct decrease ; further, it is not proven that the preliminary increase is due to excitation of ^he motor areas, since the nerves or muscles themselves may instead have been affected. Krae- pelin concluded from his experiments that motor activities were heightened by alcohol in small amounts and de- pressed by larger quantities, but that the mental activities were lowered for a period of twelve to twenty-four hours by it even in small doses. Alco- hol acts also on certain sensory centers, reducing pain. Marchiafava was the first to call attention to primary degeneration of the nerve fibers in the corpus cal- losum and commissure in men with alcoholic psychoses. The clinical pic- ture in this condition is that of a gradually developing feebleminded- ness, with perversion or deadening ot the moral sense; there may also be tremor and disturbances in speech, etc. Guizzetti (Riforma Medica, Apr. 24, 1915). Blix's test of the orientation capac- ity of the hand as a means of de- termining the amount of disturbance induced by small amounts of alcohol was applied by the writer. The test amount of alcohol was always 5 c.c, taken before rising, and the exercise was done 50 minutes later. There was always a falling off of from 20 to 50 per cent, when the alcohol was taken. C. Gyllensward (Upsala Lakareforen- ings Forhandlingar, 22, No. 3, 1917). In order to test the mental effects of alcohol, dotting machines were used for "attention" and lists of re- lated words for "memory." It was found that the general effects of al- cohol were to deteriorate these pow- ers except under certain fatigue con- ditions, when alcohol improved both powers; opium, on the contrary, im- ALCOHOL (SAJOUS). 491 proved both powers, whether under normal or fatigue conditions. The fatigue was engendered by loss of sleep for 3 nights. The tests were made every day. The more dilute the alcohol, the weaker the effect; alcohol taken after a meal had a much less evident result than when taken 4 or 5 hours after a meal. Smith and McDougall (Trans. Brit. Assoc. Adv. of Sci.; Med. Rec, Oct. 2, 1920). After the initial stage of apparent stimulation, the actual depressant action of alcohol on the nervous system is no longer in doubt. Soldiers have been found to march better and remain stronger without alcohol than when supplied with it in moderate amounts. Large single doses produce signs of dis- tinct brain depression, passing from muscular inco-ordination, with imper- fect speech, impaired sensibility, and somnolence, to a state of unconscious- ness similar to that of ether and chloro- form anesthesia. The spinal cord is depressed by alcohol even before the unmistakable signs of cerebral depres- sion occur, as shown by the early' muscular inco-ordination (apart from disturbances of equilibrium) and dimin- ished reflex irritability. The functions of the bulbar centers, however, are not markedly affected until late. On the peripheral nerves alcohol in large doses was found by Dogiel to exert a pro- nounced depressing effect in dogs. Motor nerves are believed to withstand this effect longer than sensory nerves. In the frog the response of the motor nerves to stimuli is at first increased when the vapor of alcohol is brought in contact with it, but the usual depressant action soon follows. At the Nutrition Laboratory of the Carnegie Institution an exhaustive experimental study of the physiologic consequences of the ingestion of small doses of ethyl alcohol in man showed that it induced no facilitation of the motor processes, but that the depression of the simplest forms in the finger and eye movements seemed to be one of the most char- acteristic effects of alcohol. It is ex- actly these effects which were found to harmonize most closely with the average of all the effects for the sev- eral subjects studied. F. G. Benedict (Jour. Amer. Med. Assoc, Apr. 29, 1916). Circulation. — Although the pulse- rate is commonly increased after the use of alcohol in considerable amount, Jacquet believes that where the subject can be kept free from external exciting influences, no such change in the heart- action is produced. The results of ex- periments intended to develop the action of alcohol on the heart have been con- tradictory. It is thought by many that the mammalian heart is slightly stimu- lated by alcohol unless given in large amounts, when it is depressed (Dixon and Bachmann, Wood and Hoyt, Loeb, Bachen). Alcohol in 2 per cent, strength passed through the coronaries of a cat's heart does not cause arrest of cardiac activity (Loeb). Other experimenters conclude that alcohol causes no increase in the work per- formed by the heart. According to Cushny the preliminary action of alco- hol is to weaken the heartbeats. As for the blood-pressure, moderate doses have usually not been found to alter it. The advocates of primary cardiac stimulation by alcohol account for this by the dilatation of the peripheral blood-channels, which is often manifest in the flushed face, injected conjunc- tivae, and heated skin surfaces observed after the use of alcohol. The speed with which the blood courses through the vessels is thereby increased (Hem- meter, Wood and Hoyt). Whether the vascular dilatation is due to an action 492 ALCOHOL (SAJOUS). on the vasomotor centers or on the vessels themselves has not as yet been determined. The results include dis- turbances in the cerebral circulation ; the brain may be the seat either of marked hyperemia or of anemia (Claude Bernard). Certain experi- menters have at times observed in- creased blood-pressure due to alcohol ; thus Kochmann noted in man a rise in the pressure upon the exhibition of 5 to 10 c.c. (1>4 to 2y2 drams) of abso- lute alcohol. Such an elevation of pressure mii^ht be due either to a direct stimulating efifect on the vaso- motor centers, or, as many believe, to a reflex effect on these centers due to irritation of the gastrointestinal mucous membranes. Report concerning a series of mano- metric blood-pressure tracings show- ing the effect of alcohol on dogs. By mouth it caused a marked rise in blood-pressure, with increa-ed a'lipli- tude and a constant, or slightly slowed rhythm of heart beat. This rise gradually passed off in 5 or 10 minutes. By whatever method ad- ministered, alcohol, circulating in the blood, causes a gradual, progressive lowering of blood-pressure with de- crease in amplitude but increase in rate of heartbeat. Clyde Brooks (Jour. Amer. Med. Assoc, July 30, 1910). Though whisky raises for a few moments the systolic blood-pressure, it decreases secondarily cardiac effi- ciency, raises disproportionately the diastolic pressure, and lowers the pulse pressure. C. C. Lieb (Jour. Amer. Med. Assoc, Mar. 13, 1915). The writer found experimentally that when alcohol is given orally to an unanesthetized animal there is a rapid rise in blood-pressure and res- piratory rate and an immediate return to normal. This is due to local ac- tion. Given intravenously, gradually', in quantities sufficient to kill in 1 or 2 hours, no effect occurs until just before death, when a rapid fall of pressure takes place. When given through a stomach tube there is no effect. When it is given intravenously without excitement in the normal dog, no stimulation of the heart or respiration can be observed. Hyatt (Jour. Laborat. and Clin. Med., Oct., 1919). Excessive amounts of alcohol cause a pronounced fall in the blood-pressure, since they depress both the heart and the vasomotor center. They have also been observed in animals to slow the heart action, and even produce cardiac arrest, in much the same manner as does chloroform. According- to Pou- chet, the secondary fall of blood-pres- sure is due largely to stimulation of the inhibitory pneumogastric centers; the pressure may, indeed, at a certain stage of the poisoning be brought al- most back to normal by section of the vagi. The ingestion of alcoholic bever- ages, even in small amounts, during or just after work, in which calcium cyanamide is used, induces special symptoms illustrated in the following typical case: An emphysematous worker, aged 55, who was occupied in breaking up cyanamide, took 0.3 liter of red wine at 11:25 a. m. In 3 min- utes the pulse rate rose from 69 to 104, the blood-pressure fell from 160 to 110, and the rate of breathing rose from 16 to 22. Already in the second minute there was excessive vasodila- tation of the face and conjunctivae, marked pulsation of the temporals, then nausea; the man was compelled to stay recumbent, becoming faint as soon as he attempted to rise. The pressure remained 110 for an hour, then rose slowly. The signs of vaso- dilatation passed off in about an hour. The sensitiveness to alcohol from working with cyanamide lasts over 18 hours after cessation of work, though diminishing during this period: it then disappears completely, even in individuals who have long been work- ing in the factory. J. P. Langlois ALCOHOL (SAJOUS). 493 (Bull, de I'Acad. de med., July 2, 1918). Blood. — Large amounts of alcohol must be present to cause perceptible changes in the blood in a short space of time. Foguet claimed to have ascer- tained that intoxicating doses, taken daily, were without effect. Pouchet states, however, that under small, re- peated doses, the blood gradually under- goes fatty changes, owing to the fact that the emulsified fats entering the blood with the chyle are not consumed as normally. A research on the cholesterol and lecithin content of the blood of dogs kept under . the action of alcohol, showed ihat besides the unusually high content of the blood in these bodies, the neutral fat of the blood is also increased. There seems to be an actual mobilization of the lipoids, a lipoidolj'sis, perhaps the expression of a defensive function. Ducceschi (Prensa Med. Argentina, Oct. 10, 1918). In addition to the above changes the alkalinity of the blood is lowered, the coagulability rises, and a process of dehydration goes on, as shown by diure- sis and increased secretions generally, whereby the blood becomes relatively more concentrated, the erythrocyte count and hemoglobin percentage ris- ing. Schmiedeberg found that blood containing alcohol loses in part its oxygenating power, — a fact of con- siderable practical significance. In vitro, alcohol added to blood darkens its color, coagulates it, and causes hemo- globin to leave the erythrocytes. Such effects can only be obtained in the animal organism by the intravenous in- jection of alcohol in large doses. Under these conditions the red cells undergo marked changes in shape and color (Hayem). The fats and lecithin are dissolved, and the hemoglobin becomes dissociated from the stroma and pre- cipitated in reddish, refractile droplets. Bordet and Massart showed alcohol to have a strong negative chemotactic in- fluence on the white blood-cells, even when greatly diluted. Microscopic changes in the tissues as a result of alcohol, taken from ob- servations on animals: 1. The most marked effects are produced on the blood-vessels. 2. The cells which line the vessels are swollen and broken, and there are serious retro- grade changes in all of the tissues. The white blood-cells become swol- len and necrotic. 3. The Ij-mph- spaces become choked with broken- down white blood-cells, and the small blood-vessels are also completely blocked by plugs in detritus and dead tissue. 4. In the veins the blocking is often so severe that the vessels burst from the backing up of blood in them. The changes are always more marked in the vessels of the brain than elsewhere because they do not possess the special nerves which con- trol their calil er, as do the vessels of other parts of the body. H. J. Berkley (Johns Hopkins Hosp. Bull.; Amer. Jour, of Physiol. Therap., May, 1910). Respiration. — Volumetric estima- tions made before and after the inges- tion of alcohol have shown fairly con- clusively that, even in the absence of motor excitement, the drug causes an increase in the amoimt of air breathed. Usually the augmentation is more pro- nounced in fatigued or exhausted individuals. Considerable experimenta- tion has been indulged in for the pur- pose of ascertaining whether the drug stimulates directly the respiratory cen- ters in the medulla or whether the effect is of indirect origin, viz., through irritation of the gastric mucosa. Thus Loewy conducted experiments in which the irritability of the centers of respira- tion before and after the use of alcohol 494 ALCOHOL (SAJOUS). was ascertained through its response to an increase of carbon dioxide in the blood. The results of these and other researches have not been entirely con- clusive, but, in a general way, they tend to show that alcohol exerts, in man at least, little if any direct central stimula- tion, and therefore, that the improve- ment in respiration observed under the influence of therapeutic doses of alco- hol is probably due to a reflex effect on the centers. An additional argument in favor of the latter view is in the fact that respiratory depression occurs only under exceedingly large doses of alco- hol and at a late stage in the poisoning, tending to show that the effect of this drug on the respiratory centers is, under ordinary circumstances, not a very marked one. Yet it is well known that in the final stage of acute alcoholic poisoning the breathing becomes more and more shallow and infrequent, com- plete arrest ultimately occurring. In fever, both the respiration and the heart-rate are slowed by alcohol. This seems reasonably accounted for by a lessening of general bodily excitement through the narcotic action of alcohol, without implicating a direct depressing action of moderate doses of it upon both the respiratory centers and heart. Secretions. — Many of the secre- tions are to a certain extent activated by alcohol. The saliva and digestive secretions are increased reflexly by the local action of alcohol on the mucous membranes, as well as, probably, after its absorption, through direct contact of alcohol with the gland-cells as the drug circulates with the blood-stream. The sweat secretion is increased owing to the peripheral vasodilatation. The urine is also augmented. The question whether a direct exciting action on the renal epithelium is exerted or not has not yet been settled, though the fact that albuminuria may result from excessive doses would seem to point to an irrita- tive effect on the kidney cells. Temperature. — Alcohol in ordinary doses causes a slight fall in the body temperature (34° to 1° C. according to Cushny ), owing to the to 10 drams) of spinal fluid withdrawn. Then 1 c.c (16 minims) of a 25 per cent, solution of magnesium sulphate is injected for each 25 pounds of body weight. The withdrawal and injection should be made with the patient in the sitting posture and he should then be lowered to one of semi- recumbency. Constant attention is required for 24 hours after the injec- tion to secure nourishment and proper care of the bladder and rec- tum. The treatment produces prompt relaxation. E. A. Leonard (Jour. Amer. Med. Assoc, Aug. 12, 1916). ' A study of 76 cases in the St. Louis City Hospital, in 34 of which the only treatment was a lumbar puncture, and in the other 42 treatment was by magnesium sulphate, paraldehyde, and bromides, with digitalis if the pulse was rapid. The cases treated bj^ sim- ple lumbar puncture without medica- tion remained in the hospital on the average 3 days, the same as the oth- ers, but they left virtually recovered, whereas those treated otherwise left in shaky, nervous condition. The average amount of fluid withdrawn was 28 c.c. with a maximum of 50 and a minimum of 10 c.c; the average pressure was 109 (water) with a maximum of 220 and a minimum of 65. The iodoform test revealed the presence of alcohol with cer- tainty in 30 of the 34 cases; it was questionably present in 3, and ab- sent in 1. The Nonne-Apelt and 520 ALCOHOL (SAJOUS). Noguchi tests were positive in 29 of the 34 cases. Barnes and Hein (Jour. Mo. State Med. Assoc, Nov., 1917). The following is the routine treat- ment for delirium tremens: Cathar- sis by means of calomel followed by a rather large dose of Epsom salts, because of the efifect of sulphate of magnesium in dehydrating the tis- sues of the body. Ten drops of tinc- ture of digitalis and of nux vomica by mouth every 3 hours. In the active stage of delirium strychnine and digitaline are given hypoder- mically. This stimulation the writer believes to be perhaps the most essential part of the treatment. In severe cases spinal puncture is re- sorted to as soon as the patient be- gins to have hallucinations. The cerebrospinal fluid is always under pressure and from 30 to 60 c.c. is usually withdrawn. This procedure is followed by a rapid reduction of the delirium, especially in cases which have had preliminary stimula- tion and alkalinization. If the delirium returns, spinal puncture is repeated, and the fluid is usually found to be again under pressure. If the delirium still continues in spite of the spinal puncture, or if the pa- tient is pale and covered with per- spiration with a low, muttering de- lirium, an intravenous injection of normal saline solution is given, or better. Fisher's solutioru H. H. lloppe (Jour. Nerv. and Med. Dis., Feby., 1918). CHRONIC ALCOHOLISM. DEFINITION. — A condition re- sulting- from the long-continued use of alcohol in excessive amounts. As was stated to be the case with acute alcoholism, the quantity of alcohol necessary to cause harmful results varies considerably in different per- sons. The manifestations of chronic alcoholism are varied. Alany symp- toms due to toxemia and functional derangements closely simulating or- ganic changes are observed in the beginning. Later evidences appear of true organic disease, affecting one or more organs or systems of organs in individual cases. Thus the stom- ach, the nervous system, the circula- tory organs, the kidneys, the liver, are all common seats of special inva- sion. In many cases the symptoms are very complex, and are not such as lead to the discovery of any par- ticular organic lesion. As already stated, the alcoholism is itself some- times secondary to a neurosis of other nature, in which event complex- ity of symptoms is to be expected. Dipsomania signifies a condition, he- reditary in origin, in which uncon- trollable desire for alcohol is present at intervals only, the patient being free of alcoholic tendencies in the intervening periods. Delirium tremens is another special manifestation arising from the pro- longed effects of alcohol on the brain. It will be discussed later in a separate section of this article. SYMPTOMS. — Most cases will ex- hibit in the beginning deranged diges- tion, fermentation in the stomach and bowels, constipation or diarrhea, muf- fled heart-sounds, irregular action with high-tension pulse, and increased dull- ness over the liver, perhaps with tenderness in spots. There is very commonly trembHng, the hands are un- steady in their movements, the reflexes are diminished or absent, and there are areas of extreme tenderness over the body, while numbness of the limbs, rheumatic pains in both the lower and upper extremities, congested conjunc- tivre and retinae, and defects of both siglit and hearing are often present. The patient may complain of anorexia, insomnia, chills, and frequently talks ALCOHOL (SAJOUS). 521 about malaria as the cause of his symp- toms. The urine is hkely to be of high specific gravity, and to show albumin and an excess of phosphates. Chronic catarrhal conditions of the pharynx and larynx, dilatation of the skin ves- sels, sometimes pustular eruptions, are other early symptoms often seen. At a later period the symptoms are more likely to point to certain struc- tures of the body upon which the alco- hol has exerted its chief effect. They may be grouped as follows: — (1) Digestive System. — Chronic gas- tritis is a very frequent result of alcoholism. The patient complains of anorexia, nausea and vomiting, acute pain over the stomach, and constipa- tion. The breath is foul and the tongue coated. These symptoms, usually most marked in the morning, the subject finds to be best relieved by further use of alcohol. The relief is but temporary. however, and when it ends the diffi- cult}' is increased. Gastritis and achj-lia are the rule, but a number of factors combine to induce them, not only the liquor but the irregular meals and habits of life of persons addicted to alcohol. Achj'lia was pronounced in 50 per cent. When they enter the hospital and get regular food and rest, the stomach usuallj' rapidly recuperates and, as the gastritis subsides, the achylia subsides with it. Determina- tion of the pepsin may be important for the prognosis, as the achylia did not retrogress in the few with apep- sia. The discovery of inadequate pepsin secretion therefore prophesies permanent ach3'lia. Vogelius and Wihrup (Hospitalstidende, Mar. 15, 1916). Long-continued alcoholic intoxica- tion produces in some cases pronounced structural changes in the liver, most frequently cirrhosis, with contraction of the organ, or fatty infiltration, with increased size. The symptoms of the former are those of chronic catarrh of the stomach and intestines (anorexia, nausea, flatulence, constipation, some- times light-colored stools), — which is favored by the congestion caused in these organs through compression of the portal vessels, — together with others directly due to the same con- dition, such as hemorrhages from the lower esophagus, nose, pharynx, or even the stomach or intestines; hemorrhoids ; distention of the veins of the face, especially the nose, or of other portions of the body, usually combined with flushing due to over- filled capillaries; occasionally jaun- dice. Later there may appear ascites, edema of the right pleura or of the lower extremities. Enlargement of the spleen is common late in the disease. Fatty infiltration of the liver produces no such distinctive symptoms, since there is no portal obstruction. The organ shows a moderate increase in size, but its functions are not mark- edly altered. Fahr reports a series of 309 autopsies performed at the Hafenkrankenhaus (harbor hospital) of Hamburg on vic- tims of chronic alcoholism dying from either alcoholism alone or from other causes, no less than 98 being suicides. In nearly all the cases the alcohol had been taken in the form of spirits, not as beer or wine. The results of these autopsies are distinctly not in harmony with the conception that alcohol is a poison which produces widespread and gross anatomic changes throughout the body, or that it is a common cause of either arteriosclerosis or nephritis. Even cirrhosis of the liver is far less common in alcoholics than it is usually supposed to be, for, of the 309 cases, in but 11 was Lirrhosis the cause of death ; in 2 other bodies there was an advanced cirrhosis, but death was due to some other cause. Of 100 cases of cirrhosis in which autopsies were per- 522 ALCOHOL (SAJOUS). formed by Simmonds in Hamburg, alcoholism could be excluded in 14; in 60 it was evident, and in 26 there was no reliable information as to alcohol; therefore, it must be concluded that, while only a very small proportion of drunkards suffer from cirrhosis (about 4 per cent.), there are not a few cases of advanced cirrhosis which are not due to alcoholism, although alcohol is responsible for far more than a major- ity of all cases of cirrhosis. On the other hand, in nearly every case of habitual drunkenness the liver shows fatty changes, usually severe, but not ordinarily associated with connective- tissue increase, and this is by far the most frequent change in alcoholism. Editorial (Jour. Amer. Med. Assoc, Nov. 27, 1909). The writer from his immense ex- l)erience with wine drinkers in Italy is able to detect much exaggeration in many articles published. The actual amount taken daily and the proof of the wine are of great prac- tical significance. There is a utiliz- able limit. The use of small amounts with meals only is regarded as in- nocuous. A "small bottle" of wine which contains from 20 to 30 grams of alcohol answers this requirement. Anywhere from 40 to 70 grams alco- hol daily is regarded as the limit of safety beyond which a definite action on the nervous system may be per- ceptible. A daily consumption of from 300 to 600 grams of wine means the same thing. The writer con- cludes that a minimal use of wine is not only innocuous, but perhaps salu- tary. Bianchi (Riforma Medica, Oct. 23, 1916). (2) Nervous System. — In many- cases alcohol acts most prominently as a motor paralyzer, the control over the muscles being greatly impaired. The hands are unsteady in their movements, and protrusion of the tongue is im- perfect. Ultimately paralysis is a pos- sibility. In other cases cerebral symptoms are especially marked, the prolonged action of the narcotic having caused a gradual loss of mental power. Normal cerebral activities are replaced now by exhilara- tion, again by depression. The subject becomes sluggish mentally, weak mor- ally, and loses in memory and will power. He may also show great irrita- bility, or be in a continuous state of ex- citement. His ideals are changed, and egotistic tendencies appear. Later, evi- dences of abnormal cerebration may oc- cur in the form of varying delusions and delirium. Permanent dementia is the terminal stage in this morbid chain of events, the patient becoming in his de- lusions timorous, suspicious, and some- times grandiose. The symptoms of simple or multiple neuritis are also very frequently seen in cases of alco- holism, occasionally to the extent of permanent local paralysis (see Alco- holic Neuritis under Neuritis). Alcoholic insanity presents special characteristic features which it is not difficult, in the majority of cases, to distinguish from other analogous con- ditions. Acute cerebral alcoholism pre- sents 3 states: delirious, confusional, and stuporous. The intensity of these states varies according to whether we deal with a subacute form or with delirium tremens. The chronic form leads inevitably to dementia. In the course of develop- ment of the latter, delusions with hallucinations and illusions may and may not manifest themselves. In the latter symptoms it may some- times present a picture of any other psychosis ; this resemblance is only ap- parent, as in the majority of cases close observation will enable us to find the proper interpretations. If the symptoms characteristic of cerebral alcoholism sometimes de- velop in individuals affected with other psychoses who happen to com- mit excesses, or do so because of the perverted mode of thinking or feeling caused by the psychoses, it does not follow that alcohol is capable of ALCOHOL (SAJOUS). 523 producing these psychoses. The con- ception of alcoholic melancholia, mania, paranoia, or paresis is un- scientific. Alfred Gordon (Jour, of Inebriety, Winter, 1908-9). (3) Circulatory System. — Alcohol causes irritation of the intima of the vessels and gradual degeneration of the vascular walls. The symptoms pro- duced are those usual in widespread arteriosclerosis: vertigo, hemorrhage or thrombosis of the cerebral vessels, etc. The heart and kidneys are very likely to be involved as a result of the same changes and undergo correspond- ing alterations in function. In some instances the heart seems seriously afTected. The patient com- plains of distress and pain over the precordial region, with alternate feel- ings of exhaustion and exhilaration. The pulse is frequent, and surface con- gestion is very intense. The heart may become dilated. Blood-pressure estimates were made in a series of 150 soldiers, all aged. 42 to 43 years. Among the 16 sober subjects, only 6.25 per cent, showed high blood-pressure; of 53 moderate drinkers, 7.54 per cent, showed high pressure; of 57 heavy drinkers, 17.54 per cent., and of 24 very heavy drink- ers, 25 per cent. The conclusion is reached, therefore, that alcoholism is an important factor in the etiology of arterial hypertension. C. Lian (Bull, de I'Acad. de Med., Nov. 9, 1915). (4) Kidneys. — Chronic parenchyma- tous nephritis is not uncommonly caused by prolonged alcoholic excesses. Its manifestations include disorders of digestion, increased vascular tension, anemia with characteristic translucent pallor, tendency to swollen face and extremities, together with more or less distinctive changes in the urine. The latter consist of abnormalities in quan- tity (at first diminished, later in- creased), lower specific gravity, albu- minuria ; granular casts, sometimes fatty ; epithelial and waxy casts, and decreased proportion of urea. The late symptoms include marked weakness, general anasarca, dyspnea on exertion, and uremia. Report of observations made on a German guide in Berlin some years ago. The man regularly drank over 20 liters (quarts) of beer a day. He started with a couple before break- fast, 4 between breakfast and lunch, a couple of liters at lunch, 3 more before dinner, and the remainder be- tween dinner and bedtime. Most of it was the strong Munich beer, with 6 to 8 per cent, of alcohol. The man thus consumed over 37 ounces of ab- solute alcohol a day. Yet he did not exhibit the least sign of inebriety. The case proved to the writer's satis- faction that where alcohol is diluted 20 or 30 times with water, it is al- most non-intoxicating. In view of the enormous quantities of beer consumed in Berlin, he sought in the hospitals evidences of cirrhosis or other signs of alcoholic poisoning. He found no more than would be shown by any other city of its size. In Munich, he was told, there are some evidences of cardiac hyper- trophy, due to the strain of pumping so many gallons of fluid through the kidneys. Walter (Brit. Med. Jour., Nov. 6, 1920). DIAGNOSIS.— This is facilitated if a history of excessive use of alcohol — at times in the form of proprietary remedies — be obtainable. If not, alco- holism is suggested by the presence of symptoms .«;uch as those given in the beginning of the section on symptoms, these representing mainly functional derangements and toxic effects, but few of them being the results of organic alterations. Active treatment is then begun. Under rest, restricted diet, and hydrotherapeutic measures many of 524 ALCOHOL (SAJOUS). these symptoms disappear, leaving only those expressive of permanent lesions. A careful re-examination at the end of two or more weeks will now indicate how many of the symptoms were func- tional, and which of them seemingly were organic departures from health. The special effects of the alcohol on particular organs or systems of the body are ascertained by noting the presence of symptoms referable to them, such as have already been men- tioned under that heading. It must be admitted, however, that in many cases the symptoms will appear very com- plex and refer to no particular seat of organic disease. At this second examination the diag- nosis of the patient's psychic state can also be made with some accuracy. This should comprise a study of the pa- tient's powers of reasoning, of his ideals, of his ethical conceptions of life, of the end and object in living, of his purposes and ambitions, of the ef- fects of losses and mental strains on his character, of the dominance of cer- tain passions and unrestrained emo- tional activities, and of the presence of morbid impulses and egotism. The inquiry should extend to the every- day habits of the patient. Not infre- quently periods of unexplained absence from home and business, and of unex- pected and obscure conduct, will be revealed. Such occurrences justify the inference of the paroxysmal use of al- cohol. Often the pronounced convic- tions of the patient as to the cause of his condition are significant of the use of spirits, which he denies. The diag- nosis can then be made with great clearness not from what he says, but from the facts he conceals or appears to be trying to cover up. Material assistance will sometimes be derived from a study of the family history and past medical history. He- reditary tendencies, the diseases of childhood, profoundly exhausting fe- vers, and injuries to the body may all be of importance in reaching a decision. The heredity element in inebriety is considerable and is undoubtedly a powerful predisposing- cause in in- ebriety. A history of decided intem- perance in the parents existed in over 40 per cent, of the writer's 700 cases, while 15 per cent, gave a history of defective ancestry; insanity, neurop- athy, drug addiction or tuberculosis being present on the maternal or pa- ternal side. Approximately 5 per cent, of the patients showed pre-ex- istent mental symptoms which could be differentiated. Some of these were distinct cases of psychasthenia, others were of the milder forms of manic- depressive insanity. NefT (Boston Med. and Surg. Jour., June 16, 1910). The inlluences and conditions sur- rounding the subject at the period of puberty, the effects on him of losses and failures early in life should likewise be ascertained, since they may have a marked bearing on the establishment of vicious habits. If alcohol has been taken, no matter how moderately at first or at what long intervals, its in- fluence upon subsequent morbid devel- opments should be given due consider- ation. Where the symptoms are complex and the diagnosis obscure, it is usually safe to give prominence to alcohol as a causative factor. In many such cases alcohol is used to conceal the taking of other drugs. The diagnosis can then only be a tentative one, the strong probability of an alcoholic neurosis be- ing, however, kept in mind. It may have to be altered at any time upon the discovery of new facts in the patient's history or in his present condition. ALCOHOL (SAJOUS). 525 PATHOLOGY.— In this are in- cluded changes in a large number of organs and tissues. It has been shown, indeed, that alcohol has de- structive effects on protoplasm in general. Hence, cellular elements of all kinds are open to its action, though it has been recognized that it is the most highly differentiated cells, such as those of the nervous sys- tem, which are the most easily affected. Its influence on the cells is exerted by reduced oxidation and altered metabo- lism. Destroyed cells, in virtue of a low-grade inflammatory process it produces, are replaced by connective tissue. The effect of alcohol in dimin- ishing oxidation is most prominently expressed in the failure to oxidize fats normally, with consequent accumula- tion, as in the liver and subcutaneous tissues. PROGNOSIS.— This is generally very favorable. Statistical studies in well-conducted institutions show that at least one-third of all the cases are permanently restored. The state- ments that 90 per cent, are cured have reference to present conditions, and are probably true for a limited time. On the turn of the drink cycle relapse occurs, and later recovery. The largest insurance companies in America and in England show statis- tically that the average mortality rate among total abstainers from alcohol is 68.4 per cent, of the expected rate, whereas that of the non-abstainer is 91.5 per cent., a difference of 23.1 per cent. This means a reduction of two and a third 3-ears in the average life of a non-abstainer. W. E. Porter (Med. Rec, Oct. 20, 1915). Statistics of cure are unreliable. In the treatment by gold chloride 95 per cent, were claimed to be cured. At the end of one year after treatment 55 per cent, had relapsed. At the end of the second year another 20 per cent, began to drink again. In the third only 10 per cent, continued temperate and free from spirits. On the other hand, at Binghamton, N. Y., where the first exhaustive study was made of the sub- sequent history of 1100 patients, ten years after they had been treated, the results showed 61 per cent, still temper- ate and well. These and other statis- tics, while open to error, clearly suggest that at least 33^/3 per cent, may be rea- sonably considered permanently re- stored. The future of the inebriate depends largely on the removal of the exciting causes, whatever they may be, and their avoidance in the future. In a certain number of cases there is a complete cessation and physiological change in the organism in which the impulse to use spirits passes aw'ay forever. This is now well known. It cannot be pre- dicted, but it occurs so often that we cannot but credit the results to greater knowledge, and to the use of more ex- act means in the treatment. It may be stated that the prognosis is always good, even in cases that have apparently reached the terminal stage. This prediction refers specifically to the craze for alcohol. This dies out, is overcome by drugs and rational treat- ment, while other conditions of degen- eration may remain. The alcoholic or inebriate is a com- pound of a great variety of causes, the removal of which brings about cure. Sometimes those causes are very insig- nificant, sufficiently so, in fact, to be readily overlooked. The use of tobacco changes the prognosis greatly, according to the writer, who has arrived at these con- clusions against his previous preju- dices. Among those alcoholics who 526 ALCOHOL (SAJOUS). have otherwise a good prognosis, the chances are even that he will return to alcoholism if he is a cigarette smoker. If he smokes a pipe or cigar the chances are about 3 to 2 that he will not return. If he does not smoke at all the chances are about 8 to 2 that he will not return. Lambert (Boston Med. and Surg. Jour., Apr. 25, 1912). TREATMENT.— This resembles the prognosis in uncertainty and wide variations, indicating beyond ques- tion that the subject has been scarcely touched. Both hospital and home treatment, and even moral measures, show examples of permanent restora- tion. The field is very wide and largely unknown. Soon after prohibition was en- forced, the deaths in Petrograd dur- ing the first 4 months decreased by 50 per cent, and for some months even more so. During the 3 months preceding the writer's paper, how- ever, it had risen again to the for- mer standard, or even higher, owing to the drinking of denatured alcohol, furniture polish and other substitutes for vodka. Therefore the effects of prohibition are not decisive. Xovo- selsky (Roussky Vratch, No. 15, 1915). Home Treatment. — First, there is the home treatment, i.e., care given to the patient in his own home by the family physician. It is evidently pos- sible to restore many persons, partic- ularly if they give their full assent and co-operation and carry out the meas- ures laid down for them. Home treatment requires implicit confidence in the medical adviser, and should consist 'of the absolute with- drawal of spirits and the use of means and measures to restore and relieve the conditions of starvation and poisoning present. While the causes differ in each case, their removal and the after-treatment are substantially the same. Thus, one whose living, both in regard to nutri- tion and rest, is bad requires a change. Nerve rest and regular diet must be a part of the treatment. In one who has become poisoned by spirits and highly stimulating foods, the withdrawal of these agents and rest are essential. Probably hy- dropathic measures to insure elimina- tion by means of the skin represent the most effective method of treatment. Many of these patients are suffering from delusional egotism and inability to recognize their condition (con- stantly overrating their strength), and are unwilling to use the means so evident to others. The family physician should be dogmatic and ex- act the use of means and measures that will break up the impulse to use spirits. He should treat the pa- tient mentally as well as physically, and the danger of the situation should never be minimized; he should not permit the patient to think that he can depend on his own will to over- come his diseased impulses. In many instances the patient is impressed with the gravity of his disorder. Pie must be urged to make radical changes in his living and conduct. If his work is indoors, a change to out-of-door life is requisite. If he has neglected proper exercise, this should be ar- ranged for in some satisfactory- way. The writer has employed hypnotic suggestion in 1284 cases of alcohol- ism, principally chronic. Favorable results were obtained in 80 per cent. In view of the ease of application and freedom from an\- bad effects, the author urges the general employment of this method. Zausailoff (Roussky Vratch, Aug. 4, 1912). Everything that will change the pres- ent current of thought with mental and physical activity belongs to rational ALCOHOL (SAJOUS). 527 treatment. Of course, with this, ap- propriate remedies and measures to neutrah'ze and diminish exciting causes will suggest themselves to the physi- cian. He should recognize that these are often border-line cases in which both reason and will are clouded and the patients are irresponsible. They need suggestion, forcible and em- phatic ; physical treatment, and per- sistent use of all therapeutic means. The family physician can do a great deal in this field if he will prepare himself for it and study the peculiar- ities of the patient. Office Treatment. — This is equally promising in results where the patient is recognized by the physician and his condition understood. Drug treatment forms a very important part of the means to bring relief. Probably the most practical drugs are combinations of strychnine and atropine, given at short intervals for a few weeks, then replaced by some other agent. Favorable report of treatment, es- sentiall}^ that first proposed by Mc- Bride, which consists in the hypo- dermic injection of atropine and strychnine twice or thrice daily for a month or six weeks, with attention to general hygienic condition, and tonics by mouth. Patients were told that success depended on regular at- tendance. The writer reports 7 cases, all presenting marked degrees of al- coholism. In 5, treatment was com- menced in September, 1905; July, 1907; March, 1908 (2 cases), and July, 1909, respectively. These cases had remained cured up to date. W. Asten (Lancet, Nov. 6, 1909). Reference made to Ferran's anti- alcoholic serum, obtained by adminis- tering wine to horses. The serum is collected when the animal presents reactions on the part of the system corresponding to those of acute al- coholism. The serum was tried clin- ically in chronic alcoholics. Subcu- taneous injection of the serum seemed to afford to the system improved powers of resistance against intoxi- cation. The patients experienced a marked sense of euphoria after the injection, and were enabled to react against the exhaustion or "suppres- sion neurasthenia" arising from com- plete cessation of alcoholic imbibi- tion. Berillon (Prasse med., Dec. 6, 1919). The impulse to drink may be effect- ually controlled by small doses of apomorphine given hypodermically or by the mouth. Concentrated aqueous infusion of quassia given every hour very quickly breaks up the drink im- pulse, and frequently destroys the taste for tobacco, vrhich is often a very important factor in the use of spirits. In the ofiice treatment care should be exercised not to substitute for spirits narcotic drugs that are likely to produce poisonous effects if taken without caution. Chloral hydrate is one of these drugs, commonly admin- istered, but it is unsafe and danger- ous ; also many forms of opium and its derivatives. Humulus is a narcotic of great power at times, and is often an excel- lent substitute for spirits. It is not wise to give tinctures to patients who come to the office for treatment. Give infusions always. Salines are very practical measures and can be given freely without risk. Office patients of this class want remedies that will impress them at once ; hence, the physician must study the drugs whose efifects are more or less certain. Sodium bromide is a favorite drug, and can be used with safety ; only, the physician must realize that it is cumulative in its ac- tion, and that baths, cathartics, and 528 ALCOHOL (SAJOUS). diuretics are to be associated with its use constantly. Office patients should be urged to take daily baths and exercise in the open air, but should be impressed psychically with the need of avoiding causes which lead or predispose to exhaustion. It is impossible to spec- ify particular drugs and a plan of treatment applicable to every case. The conditions vary so widely and the active and exciting causes de- pend on so many circumstances — sur- roundings, occupation, success or failure in life, diet and social influ- ences, rest, etc. — that each case be- comes a law unto itself, and requires a very close study of the conditions present. Hospital Treatment. — This is far more successful, particularly in ])er- sons who have reached the later stages of degeneration. It is a common ex- perience to have persons go to a hos- pital or sanatorium and recover from the immediate effects of spirits, and have a period of rest, change, and thor- ough elimination of the active exciting causes. They can then return to the family physician and remain under his care for an indefinite period. It often happens that hospital treatment and re- straint is the only measure that has any promise of permanency. Such hospital treatment is efl'ectual by combining hydrotherapeutics and sanitary appliances with hygienic measures specifically adapted to meet the wants of every person. Drugs are very essential adjuncts and aid materially in restoring the vigor and metabolism of the body. Diet and exercise are also very im- portant remedies. These, with nerve rest, change of thought and surround- ings, are followed by restoration. and where these measures are con- tinued over a certain length of time the cure is permanent. The actively working inebriates and alcoholics who are carrying loads of responsibility need hospital-homes in the country or by the seashore where absolute rest and quietness can displace their usual unhygienic ac- tivities. The diet, exercise, baths, electricity, tonic drugs, new duties, and new conceptions of their actual conditions must be forced upon them and become a part of their everyday life. Here psychic therapeutics comes in as a very important means of treat- ment, and as a supplement to other and physical remedies. A sanatorium hospital will supply these needs, af- ford a clear knowledge of the pa- tient's condition, and train him in the conduct he should observe in the future. Stress laid on distinction between the willful and the will-less drinker. The former are men of great energy, who firmly believe they can protect themselves from all abuse of drink. The habit is thus readily acquired and is associated with an imperious daily craving. When they seek to resist it they only defer it by some hours. They then deliberately weigh the apparent gains with the sacrifices and make a choice. The problem is a very old one, and the wise man has often played a trick on his subcon- scious self and its burning desire rather than test his will too openly. Thus Cesar Borgia, after having be- come a heavy addict to wine, reduced the capacity of his glass by the cumu- lative addition of drops of melted wax until he had weaned himself from the desire. A more rapid process con- sists in rendering the drink nauseat- ing by the addition of ipecac. The psj'chology of the willful drinker is best explained by the creation of a ALCOHOL (SAJOUS). 529 second personality through the ad- diction, which is subject to its own laws. While the strong subject may become an aboulic as a result of pro- longed addiction, there are others who are aboulic by nature, and who put up no struggle at all. These subjects are best adapted to psycho- hour or two at a time, then be rubbed down and recline in a cool room, ex- cellent effects will be obtained. If he will not, an ordinary hot bath should be followed by a vigorous hand rubbing and reclining in bed. If the desire for spirits continues and therapeutic management Jaguaribe the depression is not marked, ^30 (Bull, med., Mar. 17, 1920). There are many hospitals and sana- toria with varied measures of treat- ment, but in none of those worthy of confidence are there any specifics en- veloped with mystery. The treatment has passed beyond the empiric stage, and is now as thoroughly fixed vvith its positive results as that of any other disease, and there are no specifics or combinations of drugs that can effectually check the drink impulse unless at the peril of its breaking out again with greater force. GENERAL TREATMENT.— Ev- ery inebriate is toxemic, and every attack of drunkenness is a period of exacerbation of this toxemia. The first measure is to withdraw the spir- its and remove the poison by stim- ulating the bowels and the skin to insure its elimination. Calomel, either in a large dose of 10 grains or a small dose of 1 grain every two hours, until 6 or 8 grains are taken, together with salines, are the most effective cathartics, and should always be used at the beginning. If the patient objects to the sudden removal of alcohol, and his condition borders on delirium, ^4o of a grain of apomorphine hypodermically should be given as a relaxant. This will be followed by vomiting, free perspira- tion, and sleep. On awakening a hot bath of the temperature of 105° or 110° should be given. If the patient will consent to lie in the bathtub for an grain of strychnine with %oo of atro- pine should be given every two hours. To get a man on his feet with a clear brain, and with the craving for nar- cotics removed, a mixture of drugs given to the writer by Mr. Charles B. Towns has proven of value. It con- sists of a mixture of 15 per cent, tinc- ture of belladonna, 2 parts, and 1 part each of fiuidextract of xanthoxylum and fluidextract of hyoscyamus. From 6 to 8 drops of this are given every hour, day and night, until either the patient shows symptoms of bella- donna excess or, with the cathartics about to be described, the patient has a certain characteristic stool. This dose of the mixture is increased by 2 drops every six hours, until 14 to 16 drops are being taken ; it is not increased above 16 drops. Usually an alcoholic can be given 4 compound cathartic pills (U. S. P.) at the same time that the specific is begun. After the mixture has been given for fourteen hours, a further dose of C. C. pills is given, either 2 or 4, depending upon the amount of action obtained through the use of the previous dose. If these have acted very abundantly, only 2 are now necessary. At the twentieth hour of the mixture 2 to 4 more C. C. pills are given, and after these have acted, should the patient begin to show abun- dant green movements, an ounce of castor oil should be given, and a few hours later the characteristic thick, green, mucous, putty-like stool will appear. Usually the mixture has to be continued, and at the thirty-sec- ond hour 2 to 4 C. C. pills are again given, and a few hours later the cas- tor oil. The mixture can then be discontinued. Of course, in treating alcoholics X— 34 530 ALCOHOL (SAJOUS). one finds in tlie majority of cases the necessity to stimulate them and to give them some hypnotic, but this can be done without interfering with the hourly administration of the above. Alexander Lambert (N. Y. State Jour, of Med., Jan., 1910). The belladonna treatment properly given will totally eradicate the phys- iological craving for narcotic drugs, including alcohol. To secure perma- nent results it is necessary to pay as much attention to the after-care in both alcoholic and drug cases as is given to the derivative treatment. This after-care consists in regular supervision over several months and a thorough understanding of the needs of the patient by both himself and his friends. The treatment con- sists in the hourly administration of a mixture of belladonna, hyoscyamus, and xanthoxylum, in connection with increasing vigorous catharsis at stated intervals. At the end of this course a so-called "typical stool" is obtained, and the patient emerges into a very unusually comfortable condition with little or no craving re- maining. There are several points to be noted about this vigorous deriva- tive treatment. The belladonna mix- ture must be pushed to the physio- logical limit and not beyond. Atro- pine poisoning must be sighted, but not reached. To fall short of this point spells failure to actually ob- literate the craving; to overstep it intimidates the patient. Ross Moore (So. Calif. Pract., July. 191 H. If the restlessness and excitement continue, repeat the apomorphine i^ /4<)"te^^'^ doses every two hours. Should the stomach be irritable, use hot and cold fomentations over it, and give carbonated waters, usually Vichy. The patient should not take any food, for, as a rvtle, digestion is impaired to the extent that food can- not be assimilated. If the patient is restless and insists on moving about, have an attendant go with him and walk him until he shows fatigue, then bring him back and give a hot tub bath or shower with apomorphine and strychnine. Never give chloral or morphine. The latter may be used under special circumstances, but the former is con- traindicated. For the insomnia lupu- lin, valerian, cannabis indica, and other vegetable narcotics may be given, but never in the form of tinc- tures. Often some of these drugs produce sleep at once. Otiiers have little or no effect and should not be given. The size of the dose will depend upon the apparent sensitiveness of the pa- tient to the effects. Occasionally, where there is a tend- ency to delirium, bromide of sodium in from 50- to 100- grain doses may be used. Not more than 3 or 4 doses at intervals of three hours should be given. After giving this drug the patient should take a hot bath, which has the effect of producing more rapid absorption of tiie salt. Some- times a salt bath is preferable to plain water, if there is much de- pression. Tn the severe types of acute alco- holic delirium that have come under observation, 64 cases have all given evidence of a severe acid intoxica- tion. The sj^mptoms represent the effects of the alcohol on the nervous system and liver, and the pathologic changes maj' range from simple edema to severe degenerative changes of the fatty type. Any treatment, to be of service, therefore is indicated in the stage of edema. After experi- mental work with various salts that have the power of dehydrating edematous tissues, he devised a mix- ture of sodium bromide, sodium chloride and sodium bicarbonate that could be used in large quantities in- travenously without producing the ALCOHOL (SAJOUS). 531 toxic effect of bromide as ordinarily given in large doses. As the severe tj'pes also suffered from starvation acidosis, glucose in high concentra- tion was also used intravenously; this not onh- furnished an available carbohydrate that was readily utilized by the body, but in 30 per cent, con- centration produced marked dehy- drating effects on the central nervous system. In the preparation of the solutions 5.8 Gm. (l-?io drams) of chemically pure sodium chloride and 8.4 Gm. (2Vio drams) of chemically pure sodium bicarbonate were boiled in 120 c.c. (4 ounces) of distilled water and filtered through paper, then placed in a flask and reboiled. In addition 10.2 Gm. (2^ drams) of chemically pure sodium bromide were boiled in 30 c.c. (1 ounce) dis- tilled water, filtered and reboiled. These may be kept ready for use, and when needed are added to 850 c.c. (281^ ounces) of either freshly distilled water or tap water that has been filtered and boiled. Under no circumstances should old distilled water be used, as it has been found that it produced severe chills. This mixture is heated to about 110° F. (43.3° C.) and is ready for use. Both of these solutions must be given verj- slowly, from 20 to 30 minutes being taken for the 1250 c.c. (2^ pints) or 1000 c.c. (2 pints) employed. A small percolator, such as is used in giving salvarsan, with rubber tubing and needle attached, is all the ap- paratus that is needed. The mortalitj' was lower, 9.3 per cent.; the time of detention less, an average of 2.63 days, and the period of delirium much shortened. The patients ate better. The desire for alcohol was abolished, at least for the time being. J. J. Hogan (Jour. Amer. Med. Assoc, Dec. 16, 1916). Cinchona bark in infusion has a very good effect, and infusion of quassia chips is another remedy of great value, but for the acute stages hot water, hot baths are most prac- tical. In the course of a day or so a disgust for spirits begins. In the mean time salines should be given and the bowels kept loose. The strychnine combination should be kept up. and should the atropine symptoms appear the size of the dose ■diminished. Food should be taken very sparingly for the first t\vo days. After that a diet rich in cereals and malted milk may be given. As a rule, milk is not a good diet for these cases. Coffee and tea may be used according to the taste of the patient. Exercise in the open air and reclining in a cool room, with nerve rest, are very essential. The disposition of the patient to eat inordinately should be suppressed. If there is a tendency to constipation, mineral waters that are laxative on an empty stomach should be given. According to Hall caffeine is al- most a specific in alcoholic toxemia. This drug in doses of 1 to 2 grains every one, two, or three hours will usu- ally, in from twenty-four to forty-eight hours, quench the thirst or craving for alcohol to such an extent that the most confirmed habitues will voluntarily abandon its use. Elimination through the skin, bow- els, and kidneys should be the main purpose of the treatment, all w^ith proper nutrition and rest. Where there is a history of specific disease, mercury or arsenic in small doses is required. \\'hen the paroxysm sub- sides and the patient is restored, the great question becomes to determine the exciting causes which produce the return of the drink craze, and as- certain their periodicit\\ In most cases it is wise to discon- tinue the strA'chnine compound and continue the free use of baths, care- 52>2 ALCOHOL (SAJOUS). fully regulated diet, with salines, for some time, until evidence of the re- turn of the drink craze appears. If the patient keeps in close touch with the family physician his diges- tion, nervous symptoms, and habits of living can be studied and properly treated. Where possible, Turkish baths, with prolonged rest afterward, should be given at least once or twice a week. If the physician can secure the full confidence of the friends as well as the patient, and impress upon him the necessity of extraordinary care and the methodical use of hydro- pathic measures, a great deal can be accomplished. In the country, baths may be im- provised in a tub, and water falling on the patient in a narrow stream has an excellent sedative effect. Hot packs or sheets wrung out in hot or cold water covering the body, over which are spread dry blankets, pro- ducing intense or rapid perspiration, are often most valuable. The physician should always study the digestion of the patient and de- termine the states of acidity or alka- linity of the stomach and correct them as required. Exhaustion and depression fre- quently precede a drink impulse. Small doses of ipecac, ^ of a grain given at intervals of two hours, pro- duce a pronounced relaxing effect, and where the patient has high-ten- sioned arteries and excitable pulse this is an excellent remedy. Quassia chips in a concentrated so- lution are almost a specific for the drink craze, but they must be given in large doses at intervals of an hour or so, and followed b}^ free use of ca- thartics and baths. Quinine has some value, particularly where there is a history of malaria, but it should not be used more than about two weeks. All such cases are self-limited and will recover with the use of hygienic measures. The great vahie of the physician is to determine and remove the causes and, where there is a peri- odicity in the return of the paroxysm, to have the patient under treatment and anticipate this condition. The treatment of drug and alcohol habitues with hyoscine will remove the desire for these drugs, thus elim- inating the element which prevents the patients from abstaining by force of will power. Having lost the de- sire, they do very well without in- toxicants or the drugs, as shown by the increase in appetite, gain in flesh, and their general improvement. The question of relapse lies entirely in the sincerity and environment of the patient. The favorable alcoholic ad- dicts are those who earnestly desire to discontinue the use of intoxicants and are willing to change their mode of living and environment, but who cannot until relieved of the craving for liquor. Relapse in both drug and liquor cases is not due to a desire nor suffering after the treatment, but to their curiosity to test the necessity of total abstinence, or to the tempta- tions of social life. A single dose of the drug or drink of liquor, even af- ter 1 year of total abstinence, is very apt to start the craving, resulting in a condition which is no better than before treatment. This method may prove a valuable treatment in appar- ently hopeless cases of opium poison- ing. Interesting experiments along this line might be carried out. The one contraindication for this treat- ment is the presence of Bright's dis- ease. No patient should be treated unless put to bed and watched by competent nurses day and night dur- ing the first week. Riewel (Monthly Cyclo. and Med. Bull., Oct., 1909). [The craving for stimulants is mainly due to the depression of the endocrins fol- ALCOHOL (SAJOUS). 533 lowing their abnormal excitation by alco- hol overdosage. The stage of excitement which typifies excessive metabolism and high vascular tension is replaced by vir- tual failure of the circulation of which the sympathetic (chromaffin) system, which mcludes the adrenals, sustains oxygena- tion, metabolism and also vascular tone particularly insofar as the arterioles are concerned. Hence the danger of too sud- denly withdrawing alcohol in such patients. Strychnine, Yio grain (0.0016 Gm.), to stimulate the adrenals, posterior pituitary, Vio grain (0.0065 Gm.), to raise the vas- cular tension, and suprarenal gland 2 grains (0.13 Gm.), in one capsule t. i. d., are efficient unless excitement prevail. In the latter case hydrobrotnide of hyoscine, V200 grain (0.0003 Gm. ), hypodermically, which owing to its stimulating action on involuntary muscles tends to constrict the dilated arterioles, followed by potassium bromide 30 grains (2 Gm.), to inhibit the irritability of nerve centers, should first be administered. C. E. de M. S.] In delirium, opium and its deriva- tives and many of the other druirs that are powerful narcotics should be avoided. All proprietary drugs are dangerous, and should be condemned no matter what the experience may be. Every physician is capable of do- ing- far more for the relief of this con- dition by adapting the remedies to the particular case than by any widely exploited compound. A law, dealing with the repression of public drunkenness and the super- vision of saloons, has been promul- gated. It imposes on persons found in a manifest state of drunkenness on the streets a fine of from 1 to 5 francs for the first ofifense. The second oftense is punishable by from 1 to 3 days' imprisonment, and a third offense, when occurring within the first 12 months, is punishable by imprisonment for from 6 days to 1 month or a fine of from 16 to 300 francs. Any person who is convicted twice may be deprived of his elec- toral and civic rights for 2 years. The law fixes an analogous penalty for such dealers as shall serve liquors to minors (under 18), and dealers who are fined more than once will be liable to closure of their establish- ments for a year or more. The sale of alcoholic liquors on credit is in- terdicted. The law forbids the em- ployment of females under 18 years of age in retail liquor establishments, unless they are members of the pro- prietor's family. Dealers who en- courage debauchery shall be impris- oned for from six days to six months, and shall forfeit their political rights for five years. Their establishments shall be closed permanently. Paris Letter (Jour. Amer. Med. Assoc, Nov. 17, 1917). ACUTE ALCOHOLIC DELIR- IUM, OR DELIRIUM TREMENS. — This is a condition of acute alcoholic poisoning, associated with exhaustion and cell starvation. It occurs chiefly in habitual drinkers, but it is also ob- served in ordinary temperate per- sons after a prolonged drinking spell. Though mostly met with in spirit drinkers, it is occasionally seen in beer, wine, and cider drinkers. SYMPTOMS.— Two forms are dis- tinguished : the traumatic and the idio- pathic. They differ little except in the prodromata. In the traumatic form, after an accident (sometimes only slight trauma) the characteristic tre- mors, etc., appear, frequently without warning. In the idiopathic form, the patient who is about to have an attack is restless, uneasy, irritable ; he sleeps badly, if at all, suffers from digestive troubles, and has little desire for food. Delirium then appears. The patient cannot rest, but must be in constant motion. He is shaking all over ("the shakes"), is consumed with terrors, continually in deadly fright of things which he mentalls sees, or of persons whom he thinks are after him for the 534 ALCOHOL (SAJOUS). commission of some crime. At other times his dread is of something ter- rible, though he cannot tell what it is. He is all the while trying to escape from these well-defined or undefined horrors, and, in the attempt to escape, fatalities sometimes occur. Hallucinations of various kinds, es- pecially of sight are most common : snakes, rats, mice, loathsome things, flames, and, in a case of the writer's, roaring lions bounding down the chim- ney, below the chairs, and rushing in at the windows. According to Liepmann, visions of animals are present in 40 per cent, of cases at most. The ■delirium is best described as one of busy wakefulness and suspicion. There is a third non-febrile, innocent form, in which the temperature does not rise above 100° F. Hallucinations of hearing are not so common, but exist in probably 10 to 20 per cent, of cases. Delusions (false perceptions concerning self) are found in from 5 to 9 per cent., — mostly delusions of persecution. Sometimes there is one hallucination, illusion, or delusion throughout ; sometimes there is a succession. The tongue is white and furred. Tremor of this organ, and especially of other muscles, is a more or less marked and generally present symp- tom. The fever is not very high, being about 100° to 103° F. If higher, it is an unfavorable omen. The pulse is soft, rapid, and readily compressed. The skin is clammy. Insomnia is con- stantly present, but usually sleep and improvement occur on the third or fourth day. In unfavorable cases the patient grows gradually worse and finally dies of heart-failure (Norman Kerr). DIAGNOSIS.— Alcoholic delirium may be mistaken for the delirium of meningitis, of typhus and typhoid fevers, and of chronic alcoholism. The history and progress of the case determine the first two, and the ab- sence or significance of thirst, tongue trembling, and tremors the third. Report of tests on 8 patients show- ing that 325 Gm. of absolute alcohol must be ingested before any appears in the cerebrospinal fluid. It appears first in the urine, and disappears early here. In 5 other cases, alcohol found in the cerebrospinal fluid gave the clue to the diagnosis. In 3 it had been responsible for the fatal cerebral hemorrhage, at least 325 c.c. of alco- hol having been ingested. In a fourth it caused irregular epileptiform seiz- ures and impulsive violence which had been ascribed to the underlying epilepsy. In the fifth case, mental impairment and tendency to ataxia in the man of 54 were explained by the alcohol found in the lumbar puncture fluid during 18 daj'S. When it finally disappeared from the fluid, all the symptoms subsided. The potassium bichromate and sul- phuric acid test of Grehant and Nicloux for alcohol was used. Le- noble and Daniel (Bull, de la Soc. Med. des Hop., Oct. 10. 1919). Pulmonary disorders ; congestion, es- pecially when of traumatic origin, and pneumonia may also give rise to delir- ium simulating that of delirium tre- mens. Fractured ribs may thus become the primary, factor of violent accesses. The same may be said of erysipelas. PATHOLOGY.— Acute alcoholism is due to gradually produced changes in the nerve-tissues, and especially to retained products of metabolism. The cerebral lesions in alcoholic delirium are of two varieties. The first is observed in all alcoholics, and is due to the alcohol itself : atheromatous de- ALCOHOL (SAJOUS). 535 generation of the vessels, the degree of Of 247 recovered personal cases of disorder increasing as the caliber of delirium tremens studied by Jacobson, the vessel is reduced. The nerve-cells 202 were uncomplicated and 45 compli- also show granular pigmentation and cated by other diseases. Although the fatty degeneration. delirium tremens cannot be regarded as The second variety is derived spe- caused by the action of the pneumo- cially from the character of the delir- coccus, it resembles, in all its features, ium, and not from the alcohol itself. It an infectious disease: it has a stage of consists in congestion, hematic pigmen- incubation — a duration of about four tation in the capillaries and nerve-ele- days ; it ends with a critical sleep ; is ments, and degeneration of the nerves accompanied by rise of temperature, and fibers of the cortlex, the precursors and almost in all cases by albuminuria, of general paralysis (Norman Kerr). and when autopsy is made the spleen According to Jacobson, delirium is generally found to be the seat of tremens occurs when a brain, deterio- parenchymatous degeneration, as well rated by chronic alcoholism, is influenced as the heart, the kidneys, and the liver, by a toxic agent, either due to the action PROGNOSIS. — In private practice of bacteria or to autointoxication from the prognosis is favorable in ordinary diseases of the digestive tract, the kid- cases; in hospital practice it is much neys, or the liver. less so. Of 1241 cases admitted to the The changes in the central nervous Philadelphia Hospital during a fixed system and spinal ganglia are quite period, 121 died. Recurrence occurs if uniform; they consist essentially, first, drinking is continued. Norman Kerr in thickening of the walls of the noted recurrence from one to five times arteries, proliferation of the connective in 104 out of 442 cases treated in a spe- tissue in the media, and dilatation and cial institution. infiltration of the lymph-spaces. These TREATMENT. — The first indica- changes are more pronounced in the tion is to remove the causative tox- cortex, and frequently lead to minute emia; this can be done by persistent hemorrhages, as many as 200 of these and active hydropathic measures, having been counted in a square centi- Hypnotics are not always necessary, meter of the cortex. The capillaries and may be dangerous. They should appeared to be proliferated, particu- be avoided if possible. The best treat- larly in 1 case, but they and the veins ment is continuous baths, showers, sa- showed no pronounced anatomical al- lines, restraint, exercise, massage, good teration. The neuroglia fibers of the air, and little or no food until the de- cortex showed, according to Weigert's lirium subsides. The following repre- new method, considerable proliferation, sents, however, the measures generally The Weigert cells were more numerous recommended in such cases : — than normal. The free nuclei, both the The patient must be kept in bed small and large varieties, were in- and carefully watched. Strapping in creased in number in the second and bed should not be practised, as the sixth layer of the cortex, and appeared restraint causes muscular movements to be accumulated around the degener- and delirium. A sheet tied across the ating cells. The spinal cord was ap- bed is preferable, as this allows more parently normal (Tromner). freedom of motion. Attendants or a ■■^36 ALCOHOL (SAJOUS). padded room is best of all. No alco- hol should be given, the strength be- ing sustained by foods, milk, sovips, etc. The immediate suppression of alco- hol in delirium tremens and the em- ployment of hydrotherapeutic meas- ures advised rather than of hypnotics; the former serve to increase and to maintain the activitj^ of the heart, although one would expect an op- posite effect. In instances of cardiac weakness stimulants, strophanthus, digitalis, camphor, caffeine, are em- ployed, and in about three days, when the delirium begins to lessen, 30 to 60 grains of chloralformamide are given; this quickly induces sleep. Thirst is controlled by bitter infu- sions. If pneumonia appears as a complication, digitalis and alcohol are administered. In these patients the prognosis is distinctly bad. Eich- elberg (Miinch. med. Woch., Bd. xx, S. 978, 1907). Potassium bromide, ]-2 dram, with tincture of capsicum given every three hours, is recommended for mild cases by Osier. Sleep is, however, deemed neces- sary by some authorities. According to Lancereaux, for example, the real chance of recovery in alcoholic de- lirium lies in sleep. The patient is, therefore, isolated in a quiet, dark, and, if necessary, padded room, no physical restraint being employed. To procure sleep the patient is given 1 to 1^ drams of chloral hydrate, with l-y grain of hydrochlorate of morphine, in an infusion of limes. If sleep does not come on in about ten minutes, from % to ^ grain of morphine is injected hypodermically. After the various alcoholic dis- turbances have subsided strychnine or nux vomica is given, followed by hydrotherapeutic measures. If there should be gastric complication, an antacid, such as sodium bicarbonate, is administered. The writer reports the result of five years' use of veronal in delirium tremens. His method of administra- tion is as follows: An initial dose of 1 Gm. is given in all incipient cases. If sleep does not follow within three hours, another gram is given. Sleep then follows and lasts six to eight hours, or even twelve. On waking the patient is clear, quiet, and feels well. If there is yet some tremor, 0.5 Gm. of veronal is given, and by evening all tremor has, as a rule, dis- appeared. If the patient remains in the hospital some time longer for other reasons, 0.5 Gm. is given every evening to insure against sleepless- ness. If the delirium is not con- trolled from the 2 Gm. as given above, another gram may be given five to six hours after the second dose. Only 3 patients have failed to respond to this treatment out of a total of 100. There were 2 deaths from doul)le pneumonia. In all the author's experience he has only seen 1 case of veronal rash, and abso- lutely no other symptoms of veronal poisoning. V. F. Moller (Berl. klin. Woch., Dec. 27, 1909). Broadl)ent, of London, has found very efficacious the following treatment of de- lirium tremens. The patient is stripped naked and lies on a blanket over a water- proof sheet. A copious supply of ice-cold water is provided, and a large bath sponge dripping with the iced water is dashed violently on the face, neck, chest, and body as rapidly as possible. He is then rubbed dry with a rough towel, and the process is repeated a second and a third time. The patient is now turned over, and the wet sponge is dashed on the back of the head and down the whole length of tiie spine two or three times, vigorous friction with a bath towel being employed be- tween the cold-water applications. By the time the patient is dried and made com- fortable, he will be fast asleep. Delirium tremens, on alcoholic basis, even in strong men of middle age. is a serious illness, with a mor- ALCOHOL (SAJOUS). 537 tality variously stated as 3 to 19 per cent. The writer treated 396 cases from 1901 to 1906 with chloral hydrate (1 to 3 grains) and with bromides. Digitalis was given only when neces- sary, and alcohol was withheld. The mortality was 9 per cent. Of the cases, 17.4 per cent, belonged to th^ type of delirium imminens. Between 1907 and 1909, 264 cases were treated almost exclusively with veronal. The drug was dissolved in warm tea. Soon after admission the patient re- ceived 1 Gm. (15 grains), and one to two hours later a second gram. If necessary, a third gram is adminis- tered within five hours and a fourth gram within twelve hours. There never was the slightest untoward effect on pulse or respiration. The mortality sank to 3.4 per cent.; the percentage of cases where the de- lirium could be prevented rose to 28. The majority of fatal cases already suffered from pneumonia. This ob- servation proves that veronal is far superior to chloral and bromides to check the attack in its incipiency, and also to prevent a fatal issue. Ernst V. d. Porten (Therap. d. Gegenwart, June, 1910; Merck's Archives, Nov., 1910). Incipient cases, with insomnia, rest- lessness, tremor, occasionally hal- lucinations, should receive large doses of hypnotics, preferably veronal; whisky should be given regularly, and ergot at frequent intervals, either by intramuscular injection or by mouth. Discontinue medication gradually, and only after all restlessness and tremor has disappeared. More advanced cases, with marked delirium, inco- ordination, usually fever, slight leuco- cytosis, and profuse perspiration, should receive veronal in moderate doses; also ergot. Ranson and Scott (Amer. Jour. Med. Sci., May, 1911). It must not be forgotten, however, that large doses of narcotics, with the cardiac depression apt to follow their exhibition, are dangerous, especially in the aged and infirm inebriates. Kerr preferred repeated doses of liquor ammonias acetatis (B. P.). Sleep, thus quietly and safely in- duced, has proved much more cura- tive than narcotics in his practice. Trional and opium, if given, should be administered cautiously. If fever is present, the cold douche, bath, or preferably the wet pack may be tried. If the pulse becomes too rapid and weak, very small doses of digitalis in aromatic spirit of ammo- nia should be given. Digitalis in large doses is dangerous (Osier, Delpeuch, Kerr). The author witnessed the collapse and death of a robust man in delirium tremens while being given a prolonged warm bath. One of his patients suc- cumbed in collapse during a wet pack, and he has consequently abandoned these measures. In treatment of 1051 cases of delirium tremens in the last sixteen years, he has made it a rule to allow no alcohol. In the first series of 486 cases the mortality was 6.37 per cent., while in the last 565 cases it has been only 0.88 per cent. He ascribes this improvement in the results to his observation of the fact that the cause of death in delirium tremens is gen- erally paralysis of the heart, and he now addresses treatment to the heart regardless of whether cardiac symp- toms are apparent or not. The agita- tion and motor excitement react on the heart, and signs of heart weakness soon become manifest. He makes it a rule to give digitalis from the very first, giving 1.5 Gm. in an infusion in the course of the day and repeating this dose two or three times. If it can- not be given by the mouth, he gives it in a rectal injection. At the first signs of heart weakness other heart tonics are used; 1 Gm. of camphorated oil is injected subcutaneously every hour or so until the critical symptoms subside. A tablespoonful of ice-cold cham- pagne every half-hovir was also found useful — the only way in which he allows alcohol. To promote the washing out of the toxins causing 538 ALCOHOL (SAJOUS). the attack, he has the patients drink copiously, and supplies them for the purpose with a drink which has the color of beer and tastes refreshing, and is taken eagerly by the delirious patient. It is merely a 1 per cent, solution of sodium acetate in water to which a little common syrup has been added. S. Ganser (Miinch. med. Woch., Bd. liv, Nu. 3, 1907). The writer ascribes the symptoms of this condition to the accumulation of toxic products, autogenous as well as alcoholic, in the blood. Accord- ingly, he aims at the removal of these deleterious substances. He gives nor- mal salt solution in large quantities by the rectum, hypodermically, or, if necessar>', intravenously. Thus the entire circulatory system is flushed with fluid to its utmost capacity, and this is then relieved by free purgation with large and repeated doses of Epsom salt. Calomel in full doses is also given. Sparteine is administered in 2-grain doses for the purpose of supporting the heart and promoting diuresis. For the delirium itself gel- semine is given every hour, or every two hours, until its physiological effect is produced; the dose advised is %5 grain. Alcohol is reduced to moderate limits, but is not entirely withdrawn: opium and other nar- cotics are condemned as not merely dangerous, but useless. Physical re- straint is also held to be not permis- sible. In 450 consecutive cases the results of this line of treatment are described as excellent, and no death from delirium tremens occurred in the whole series. G. E. Pettey (The Hospital, Jan. 15, 1910). The writer found that cases of acute alcoholic delirium of the se- verer types were suffering from acid intoxication. His treatment, there- fore, was directed towards efforts to neutralize it and to favor its rapid elimination. He emplo3'ed a mixture of sodium bromide, sodium chloride, and sodium bicarbonate that could be used in large quantities intravenously without producing the toxic effect of bromide as ordinarily given in large doses. As the severe types also suf- fer from starvation acidosis, glucose in high concentration was also used intravenously. The solution may be given once a day or every 2 hours, according to the results oi)tained. In the cases given the blood-pressure was lowered after the injections. Any existing edema, as of the brain, was reduced; all the tissues of the body and the blood were dehydrated by the action of the salts. Hogan (Jour. Amer. Med. Assoc, Dec. 16, 1916). The routine treatment for delirium tremens employed by the writer in the Cincinnati General Hospital is as follows: Catharsis is used as a routine measure, calomel, followed by a rather large dose of Epsom salts. Tincture of digitalis and tinc- ture of nux vomica, 10 drops of each, are given by mouth every 3 hours. In the active state of delirium strych- nine and digitalin are given hypoder- mically. This stimulation is the most essential part of the treatment. In mild cases the indication for alkalies is met by the use of the imperial drink with lemon juice. Prolonged hot baths and hot packs are given twice a day, chloral and bromids are given only at night, and then not more than 2 to 3 doses during the 12 hours. In ordinary mild cases of delirium tremens, uncomplicated with kidney troulde, the above treatment is sufficient and the disease runs a very mild course. In the more severe cases, and at present a routine treat- ment, spinal puncture is resorted to as soon as tlie patient begins to have hallucinations. From 30 to 60 c.c. (1 to 2 ounces) are usually with- drawn. The withdrawal of fluid is followed by a rapid reduction of the delirium especially in cases which have had preliminary stimulation and alkalinization. Hoppe (Jour. Nerv. and Mental Dis., Feb., 1918). The patient .should be carefully fed, milk and concentrated broths beinsf especially useful. If necessary, nutri- ent enemata are to be administered. ALCOHOL (SAJOUS). 539 Excellent is hypodermoclysis or the intravenous infusion of saline solution in delirium tremens, which increase the amount of the circulating medium in which the toxic materials are dis- solved, thereby diluting the poison and bathing the nerve-centers with a HDore attenuated solution of the same. The amount of circulating fluid is increased above the normal, so that the excretion of fluids through all the eliminatory channels is augmented, thereby carrying off in solution much of the contained toxins. The action of the heart is improved by the filling of the relaxed vessels. These suffice to restore the physiological equilibrium and turn the balance in favor oi recov- ery (Warbasse, Quenu). Comparison of the number of cases of delirium tremens and of trauma in drunken men during a period of municipal total prohibition with the period before it, and during a period of partial prohibition in that a sup- posedly prohibitive price had been placed on liquors. The cases of delirium tremens which had averaged 5 or 6 a week, ceased totally during the total prohibition, but the number of "drunks" was even higher than usual, the restrictive measures evi- dently failing in their purpose. It takes brandy to produce delirium tre- mens, and this is scarcely obtain- able. H. 1. Schou (Ugeskrift for Laeger, May 24, 1917). ACUTE ALCOHOLIC MANIA (MANIA A POTU). SYMPTOMS. — The patient, in a wild, ungovernable fury, shouts, stamps, strikes, or kicks, and is, for the moment, uncontrollable. The eyes roll, the face is flushed, and the veins dis- tended and engorged ; the muscles are at their highest point of tension, and are in continuous, violent action. The pulse is strong, bounding, and tumultu- ous. Though mechanically conscious, the subject is filled with "blind fury." He is carried away in a tempest of nerv- ous excitation and passion. The par- oxysms of violence sometimes last only a few minutes, at other times for from an hour to several days, with quiet intermissions. Rarely are there delu- sions, though the infuriated subject may vent his violence on the first ani- mate or inanimate object in his way. In a few cases the fury is directed against a certain person or thing. Vio- lence is succeeded by calm ; a few min- utes after a storm the temperature is normal, and during the paroxysm rarely raised. In some constitutions a paroxysm may be provoked by a small quantity of alcohol (Kerr). DIFFERENTIAL DIAGNOSIS. — It may be differentiated from delir- ium tremens by the absence of tremors, terror, hallucinations, delusions, the white tongue, nausea, and the delirium of the latter. Further, mania a potu may arise from a small quantity of an intoxicant taken in a short time, while delirium tremens is due to large quan- tities taken in rapid succession, or from smaller quantities long continued (Kerr). ETIOLOGY AND PATHOL- OGY.— Mania a potu is occasionally seen in chronic inebriates, and most frequently in periodic tipplers. In the latter it often occurs when, after an interval of abstinence, an intoxicant is freely partaken of. Some chronic inebriates invariably suffer acute mania if they drink a single glass of spirits, wine, or beer beyond their usual allow- ance. The paroxysms of acute mania resemble those of epilepsy, and a large proportion of police-court drimken of- fenders are patients of this class. The 540 ALOES (SAJOUS). symptoms are evoked by the patho- logical action of acute alcoholic in- toxication on nervous systems liable to such excitation, either congenitally or from the efifects of intemperance, traumatism, or brain-tire. According to Jones, the forms of insanity met with which result from alcoholism are: 1, amnesic; 2, delusional and, 3, chronic varieties which end in de- mentia. PROGNOSIS. — The prognosis is much more favorable than in ordinary acute mania, the paroxysm usually rapidly passing away, leaving the pa- tient exhausted and peaceful. Unless alcohol be taken again relapse is rare. TREATMENT.— But little treat- ment is generally needed in this con- dition. Non-alcoholic liquids, such as milk, iced milk, milk and soda, or saline draughts with ipecacuanha and bromides are sufficient to bring about recovery. Sometimes cold affusions and, in prolonged paroxysms, wet packs prove valuable adjuncts. AVhen violent mania is present, apo- morphine, Yg to % grain, hypodermic- ally, causes nausea and rapid sedation. If it persists, potassium bromide, in 30-grain doses every two hours, or morphine, 14 grain at long intervals, must be resorted to. C. E. DE M. Sajous AND L. T. DE M. Sajous, Philadelphia. ALEPPO BOIL. Sore. See Oriental ALOES (Aloe). — The inspissated juice of the leaves of Aloe vera or A. chinensis (Curacjao or Barbadoes aloes) or of other species, such as Aloe Perryi (socotrine aloes, East Africa) and Aloe spicata or A. fcrox (Cape aloes). The plants are indigenous in Africa and India, and are naturalized in the West Indies and along the Med- iterranean shores. PROPERTIES AND CONSTIT- UENTS.— Curasao aloes occurs in orange-brown, opaque, and resin-like masses which give ofif an odor of saf- fron and have a very bitter and some- what nauseous taste. Socotrine aloes varies in color from yellowish brown to dark brown ; its odor and taste are similar to those of Barbadoes aloes. Cape aloes is reddish brown or olive- black. According to A. R. L. Dohme, Curacao aloes is as efficient as socotrine aloes and less expensive ; the greater portion of the latter now sold is made up of the former. Purified aloes {aloe piirificata), the form generally employed in medicine, is aloes which has been softened by heating and the addition of alcohol, strained, and dried. It occurs in com- merce in pieces or in powder form. Aloes contains: 1. Aloin, a bitter, crystalline principle present in amounts ranging from 4 to 30 per cent., and composed in socotrine aloes exclusively of barbaloin, to which, in Curaqao aloes, is added the isomeric body iso- barbaloin. 2. Emodin (Kraemer), an actively cathartic principle. 3. A yel- lowish, odoriferous volatile oil. 4. A resinous material, varying according to the species of aloes. 5. Albuminous bodies. 6. Fatty substances. 7. A small amount of gallic acid. Aloin, official as Aloinum, occurs as minute orange-colored crystals or as a microcrystalline powder varying in color from lemon-yellow to yellowish brown. It has little or no odor, is bitter to the taste, and remains unchanged in the air. It is soluble in 65 parts of ALOES (SAJOUS). 541 water and in 10.75 parts of alcoliol. its Tinclnva Bcnzoini Composita,con\.-A\n- solutions turn brown on continued ex- ing benzoin, 10 parts ; aloes, 2 ; storax, posure, and wben alkalies are added 8; tolu, 4. Dose: 30 minims (2 c.c). present a dark-red color with greenish Extractum Colocynthidis Composi- fluorescence. turn, containing extract of colocynth, DOSE AND PREPARATIONS. 16 parts; purified aloes, 50; resin of — the dose of purified aloes in adults scammony and powdered soap, of each, is Yy to 10 grains (0.03 to 0.6 Gm.), 14 j cardamom, 6. Dose: 7 }/> grains the average dose being ofificially given (0.5 Gm.). as 4 grains (0.25 Gm.). .The dose of p,-/,^^ cathartica composita. aloin is 14 to 2 grains (0.03 to 0.12 u Ext. colocynthidis Gm.). Average dose: 1 grain (0.065 camp gr. i% (0.08 Gm.). Gm.) . The other official or semi-offi- "^f-^- ";"";'■;« ^^ . ^^^ ^^^ cial preparations of aloes are: — Resince jalapce .. gr. % (0.02 Gm.). PUula Aloes, containing aloes and ^^'^V'if^'!..^." '.'... gr. ^4 (0.015 Gm.). soap, of each, 2 grains (0.13 Gm.). Dose: 2 pills. Dose : 1 to 4 pills. Pilula rhei composita. Tinctura Aloes (10 per cent.), con- H Rhei pulveris ... gr. ij (0.13 Gm.). ... 1 o/A J. i ^• • Aloes gr. iss (0.10 Gm.). tammg also 20 per cent, of licorice. Myrrhce gr. j (0.06 Gm.). Dose: H to 1 fluidram (1 to 4 c.c). Olei menthce pip., gr. 1/12 (0.005 Gm.). Average dose: 30 minims (2 c.c). °°'^= ^ P'"^- . 7- , , 4, -M T7 \ ,^4.^^-,r Pilula cathartica vegetabilis, N. F. Extractum Aloes, N. r. — A watery / ... , 1 J -r-. T/ !> E-xt. colocynthidis extract, dried and powdered. Dose : /. ^^^^^^ ^^ . ^^ ^^ ^^^ to 6 grains (0.03 to 0.4 Gm.). Aver- Ext. hyoscyami . gr. ss (0.03 Gm.). age dose: 2 grains (0.125 Gm.). 5"/«f jf'^;^ •• s^. % (0.02 Gm.). ° . . Ext. leptandrce, Pilula Aloes et Ferri, N. F., contain- Resince podo- ing purified aloes, dried ferrous sul- J^}y^^' ;; ^a gr. }4 (0.015 Gm.). «= ^ . Olei menthce phate, confection of rose, and aromatic piperita: gr. H (0.008 Gm.).- •powder, of each, 1 grain (0.07 Gm.). Dose: 2 pills. Dose • 1 to 4 oills Pilula laxativa composita, N. F. r,.,' 7 (7 J. ^T I.- 1 AT T7 R Aloini gr. % (0.013 Gm.). Pilula Aloes et Mastiches, N. F., strychnines ir. 1/128 (0.0005 Gm.). (Ladv Webster's Dinner Pill ), contain- Ext. belladonnce . •£• , 1 o • /rv 1 ^ r- ^ fol gr. i^ (0.008 Gm.). ing purified aloes, 2 grams (O.lo Gm.) ; ipecacuanha: pulv. gr. Ho (0.004 Gm.). mastic, % grain (0.04 Gm.), and pow- Glycyrrhizce pulv. gr. ^ (0.046 Gm.). dered red rose, 1/0 grain (0.03 Gm.). Dose: 2 pills. Dose : 1 to 4 pills. MODES OF ADMINISTRA- Pilula Aloes et Myrrhce, N. F,, con- TION. — Aloes is entirely soluble in taining purified aloes, 2 grains (0.13 5 parts of alcohol, but only partly sol- Gm.) ; myrrh, 1 grain (0.07 Gm.), and uble in water. It is generally admin- aromatic powder, % grain (0.04 Gm.). istered in pill form on account of its Dose : 1 to 4 pills. strongly bitter taste. It acts slowly, Tinctura Aloes et Myrrhce, N. F., and can, therefore, be administered at containing aloes, myrrh, and licorice, bedtime with the expectation that its of each. 10 per cent. Average dose: effects will be exerted the next morn- 30 minims (2 c.c). ing. Aloes may be used alone, but is Aloes is also a constituent of : — oftener given in conjunction with other 542 ALOES (SAJOUS). cathartic remedies and correctives, as in several of the preparations above mentioned. Certain agents have been found to increase its effects, including bile, iron, and the alkalies. Equal parts of purified aloes and dried oxgall may be administered in a salol-coated pill with advantage. Aloin, while somewhat less certain in its action than aloes, is often considered preferable because of the smaller dose required and less lia- bility to cause "griping." It is fre- quently employed in the aloin, bella- donna, and strychnine pills, of which the official form (Pilula Laxatiz'a Comp.) has already been referred to. INCOMPATIBLES.— Aloes is in- compatible with mineral acids, iodine, silver nitrate, tannic acid, phenol, men- thol, thymol, and salicylic acid. CONTRAINDICATIONS. — It is generally inadvisable to prescribe aloes in cases of hemorrhoids, owing to its eflfect of causing congestion of the pel- vic organs; in cases accompanied by free secretion of mucous in the bowel, however, it may, on the contrary, prove beneficial. Aloes is likewise contrain- dicated in pregnancy and in menorrha- gia occurring in plethoric women. In view of its elimination, in part, through the milk, it is not available for use as a purgative in nursing women. PHYSIOLOGICAL ACTION.— In small doses aloes and aloin exert a stomachic efifect. The secretions of the alimentary tract are augmented. With largfer doses (2 to 4 grains) its well- known laxative effect is obtained, ten to fifteen hours usually elapsing from the moment of extubation until the first evacuation results. The effect is due to stimulation of the muscular coat as well as the glands of the large intestine, and is generally attended with a cer- tain amount of griping pain. Through its property of inducing hyperemia in the ovaries and uterus, aloes also has distinct value as an cmmcnagogiie. Though easily absorbed through abrasions and ulcerated areas (exercis- ing thereafter its characteristic laxative and other effects), aloes exerts no local therapeutic action. It is eliminated with the feces, slightly with the urine, and, in nursing women, with the mammary secretion. Aloin, the so-called active principle of aloes, is believed not to exert its ef- fect in the bowel until it has undergone certain changes in composition. The resulting active compound, which can be made from the pure, crystalline aloin by boiling a solution of the latter (Cushny), is probably contained in the crude drug after the crystalline aloin has been extracted. Hence, the fact that in practice crude aloes is found to act with greater certainty and speed than the principle aloin. It has been found that in human beings placed upon an exclusive meat diet aloin acts much more strongly than in persons subsisting on a mixed diet. The aloin is believed to be altered through proc- esses of hydrolysis and oxidation into cmodin (o.xymethylanthraquinone), an active constituent of many other drugs of this class, such as senna, cascara sagrada, and rhubarb, which induces the purgative eflFect. Injected under the skin or into a vein, aloin for the most part passes into the bowel, there exerting an irritant effect and inducing purgation. In the rabbit, however, in which aloin is excreted to a large ex- tent through the kidneys, pronounced irritation of these organs is produced, catharsis being, on the other hand, an infrequent result. A nephritis is gen- erally induced, in which the epithelium of the tubules is particularly involved, ALOES (SAJOUS). 543 the glomeruli being largely spared. The urine contains casts, blood, proteids, and leucoc}'tes ; it may be either aug- mented or decreased in quantity (Miir- set). UNTOWARD EFFECTS. — The use of aloes over long periods is said to favor the production of hemor- rhoids. Large doses of aloes induce burning at the anus ; sometimes blood- stained stools, painful micturition, and uterine discomfort. Dosage ex- ceeding 0.20 Gm. {3 grains) per diem, when persisted in for any length of time, leads inevitably to intestinal irritation and congestion (Pouch et). Massive single doses of aloes may in- duce general prostration with slowing of the pulse and a fall in the tempera- ture. THERAPEUTIC USES. — As a Laxative. — Aloes is most frequently used in the treatment of constipation due to intestinal atony. In moderate doses it stimulates the intestinal mu- cosa to increased secretory activity, thereby facilitating the discharge of the bowel contents. Its continued use is, however, to be avoided, since on pro- longed administration a tendency to aggravation of the disorder present is likely to appear. A characteristic feature of the ac- tion of aloes is the congestion it tends to produce in the intestinal tract (es- pecially the rectum) and pelvic organs. This property has led to its occasional use as a derivative in conditions asso- ciated with cerebral or pulmonary con- gestion, blood being thereby removed from the engorged area. Experimental work has shown that aloes, in common with other purgatives of the anthracene series, does not act as a true chola- gogue, i.e.. does not increase the amount and concentration of the biliary secre- tion. It does, however, by accelerating peristalsis, promote the removal of bile from the intestinal tract, and prevent Its reabsorption from the duodenum into the liver. For the relief of hepatic congestion, Rendu has recommended the use of aloes in combination with calomel and gamboge. The cathartic effect of aloes has been found to be greatly favored by the presence of bile, which is believed to assist by exerting a solvent action on the drug, thereby hastening its effect. In view of this observation, too, it is thought that in cases of obstructive jaundice the action of aloes is interfered with owing to the deficiency of bile. Alkalies and iron assist the purgative action of aloes. The former facilitate the decomposition of aloin, whereby a more strongly irritant and cathartic substance is formed. Iron similarly favors the oxidation of aloin. In chlo- rosis the aloes and iron combination is often employed, as in the official pill of aloes and iron. It is best, however, not to use this pill, owing to the par- ticularly marked constipating effect of the preparation of iron it contains. The pyrophosphate of iron or dialyzed iron is to be preferred. Nux vomica and belladonna, or their active alkaloids, are also frequently combined with aloes, the former to improve the tone of the intestinal muscles, and the latter to prevent "griping." The last-named effect can also be minimized by giving the drug after meals. Robin recommends the following pill as a mild, but efficient laxative : — B Aloes, Ext. of liquorice ..aa 1 gr. (0.06 Gm.). Gamboge 3^ gr. (0.03 Gm.). Ext. of belladonna, Ext.ofhyoscyanius^aa. 1 gr. (0.06 Gm.). Enough for 1 pill. Take one or two on retiring. H4 ALOPECIA (SCHAMBERG). Aloin possesses over crude aloes the advantages of smaller bulk and less tendency to cause intestinal irritation, but these are partly offset by the dimin- ished certainty and celerity of its action. In large doses aloes acts as a drastic, inducing first eructations and a feeling of weight in the stomach, then copious stools with colicky pains. Its use as such, however, is to be avoided, because of the marked intestinal irritation and congestion it causes. As a Stomachic. — In doses not ex- ceeding 1 to 1'/; grains (0.06 to 0.10 Gm.) daily, aloes improves the appe- tite and excites the gastric functions. As an Emmenagogue. — In anemic women with amenorrhea aloes is sometimes given to favor the men- strual flow. It is best given four days before the expected period, and its action is greatly enhanced by combi- nation with iron. In amenorrhea due to other causes the official pill of aloes and myrrh may be tried, the congestive influence of the active drug tending to facilitate menstruation ; good results, however, follow less often than in the anemic cases. In Hemorrhoids. — Though the use of aloes as a laxative is contraindicated in the presence of hemorrhoids, this drug, given in small doses, has been claimed by some to be beneficial in cases where the circulation in the in- ferior hemorrhoidal veins is particu- larly sluggish and the pile masses protrude, inducing tenesmus. The use of aloes in very small doses when hem- orrhoids are associated with irritation and frequent small, thin evacuations has been advocated by Fordyce Barker. C. E. DE M. Sajous AND L, T. DE M. Sajous, Philadelphia. ALOPECIA. — r.aldness ; calvities. DEFINITION. — Alopecia is a physiological or pathological deficiency or loss of hair, either partial or com- plete. The forms of alopecia may be classified as shown on opposite page. Congenital Alopecia. — This com- monly manifests itself either as a scanty growth, a development only in certain localities, or as a retarded appearance of the hair. In rare cases there may be complete absence of the hair due to arrested development of the follicles. In such cases hereditary predisposition is usually present, and there are apt to be, in addition, delayed or defective dentition, and at times developmental defects of the nails. [J. H. Hill (Brit. Med. Jour., vol. i, 1881, page 177) has described a race of hairless Australian aborigines. Jay F. Schamberg.] Case of hereditary alopecia due to hypothyroidia, occurring in 3 gener- ations, affecting equally the male and female members of the family, and limited strictly to the scalp. The affected individuals were born with a normal growth of hair which con- tinued to grow normally until about the fourth or sixth year. It then be- gan to fall out and lose its pigment, becoming completely colorless, and continued to do so until at puberty or a little later the scalp was com- pletely Itakl. In 3 children of the family under ol)servation the ad- ministration of thyreoidin, in doses of H to 1>4 grains (0.03 to 0.09 Gm.) daily, was followed by good results. Petersen (Dermat. Zeitsch., Apr., 1915). A diminution or absence of the se- cretion of the thyroid gland is known to cause the following changes in the skin: Myxedema, roughness and dryness of the skin; yellow com- plexion with a rather circumscribed redness of the cheeks, called the "malar flush"; dry seborrheic coating of the scalp, constituting at times a thick crust; dryness, lack of luster AL( )rEClA (SCHAMBERG). 545 Forms of Alopecia. I. Congenital alopecia. II. Senile alopecia. III. (a) Idiopathic. Premature alopecia. f Hereditary predis- [ position. (1) Local diseases. (b) Sj^iiptoinatic. ^ (2) General dis- eases. Seborrhea. Eczema seborrhoicum. Psoriasis. Erysipelas. ^ Lupus erythematosus. Syphilodermata. Folliculitis. Tinea tonsurans. Tinea favosa, etc. Typhoid fever. Acute Variola. Scarlatina. Pregnancy. Syphilis. Leprosy. Myxedema. Neurasthenia. Chronic intoxications. Anemia. Diabetes. Cancer. Uric acid diathesis. Phthisis, etc. Chronic ^ and wiriness and defluvium of the hair. He cites a personal case in which progressive alopecia yielded rapidly under a careful diet and 5 grains (0.3 Gm.) of thyroid gland a day. Montgomery (Jour. Cutan. Dis., Apr., 1915). Its really important and striking features, based on a careful stud}' of serial sections from different parts of the skin of a case were the fol- lowing: there were comparatively few vessels; there was 1 arrector pili muscle; 1 abortive follicle; no hair shaft; no sebaceous glands; and no sweat glands. Blaisdell, Cunning- ham and White (Boston Med. and Surg. Jour., Feb. 8, 1917). Senile Alopecia.— As the name indi- cates, this form of baldness is observed in the aged. With the atrophic skin changes that accompany senility there takes place a gradual thinning of the hair, beginning upon the vertex of the scalp, the frontal and the temporal regions, and slowly leading to a more or less complete baldness of the cal- varium. Under the microscope the cutis proper and the hypoderm exhibit thinning and atrophy. Case of periodical shedding of the hair in a woman aged 21 years. Her hair was shed every winter and grew in again in the summer. Last winter she became entirely bald, and this sum- mer her hair did not grow in again. Absence of hair existed on the general surface, which began in circular patches when she was 12 years old. H. Leder- mann (Jour, of Cut. Dis., Jan., 1904). Premature Alopecia. — This form of alopecia is encountered chiefly in in- dividuals between tlie ages of 20 and 35. G. T. Elliott found that among 344 1—35 546 ALOPECIA (SCHAMBERG). private cases of premature alopecia, 64 per cent, occurred under the age of 30. Premature alopecia may be either idio- pathic or symptomatic. In the idiopathic variety the scalp presents no abnormal condition. At first only a few hairs fall out from time to time, being replaced by a shorter or finer growth. Later these fall and are followed by still finer hairs. In this manner the greater part of the hair of the scalp may be gradually lost. The affection occurs in both sexes, although much less frequently and less com- pletely in women than in men. Heredity api)ears to be a strong predisposing factor. There is a growmg opinion that the so-called idiopathic baldness is excep- tional, and that most cases of premature alopecia are associated with seborrhea in some form. Of 344 private cases of premature alopecia studied by Elliott, 316 had seborrhea. Jackson found 75 per cent, of 300 cases due to seborrhea. The symptomatic form results from various local and general diseases. Rapid falling of the hair (defluvium capillorum) commonly follows acute diseases, such as typhoid fever, small- pox, etc. Full regeneration of the hair follows the restoration to health. Rapid and extensive loss of hair occurs with frequency in the early stages of syphilis. The hair is also thinned or lost in such cachectic condi- tions as phthisis, myxedema, diabetes mellitus, leprosy, etc. Referring to the fall of the hair after influenza, the writer points out that the temples and occiput are the areas usually chiefly affected. He at- tributes it to the toxemia, and thinks probably it is indirectly due to the toxemia affecting the trophic nerves to certain areas of the scalp. He does not recommend cutting the hair un- less that is necessary to carry out any special form of treatment. A. Pasini (Giorn. Ital. d. Mai. Ven. e delle Pelle, fasc. i, 53, 1919). Alopecia Seborrhceica. — Consider- able difference of opinion exists as to what constitutes the seborrheic proc- ess ; the comprehension of the relation of seborrliea to baldness is thereby embarrassed. Nearly all writers are agreed that dandruff has not the same significance for all observers. Sabour- aud holds that dry pityriasis of the scalp is not a depilating afifection itself, but that it is frequently asso- ciated with the true seborrhea. Many clinicians speak of an alopecia pityrodcs in which there is either a seborrhea with fatty crusts or a pityriasis with abundant scaling. Crocker does not restrict alopecia seborrhceica to the oily form: according to his experience there is either "an excessive greasi- ness of the surface from oily sebor- rhea, or fine, glistening, powdery scales, or greasy scales lying closely on the scalp and requiring to be scraped off, or yellowish, fatty matter looking like pale-yellow wax." New clinical form of atrophic alo- pecia, for which the term "pseudo- pelade" is adopted. It is a process of atrophy and sclerosis affecting the hair- covered regions of the body, especially the scalp, terminating in patches of baldness, smooth, of pseudocicatricial aspect. It seems to be closely allied to erythematous lupus and keratosis pilaris. Brocq, Lenglet, and Ayrignac (Annales de dermat., vol. t, No. 3, 1905). Analysis of 679 cases of loss of hair, chiefly alopecia simplex and alopecia furfuracea. There were, however, 86 cases of alopecia and lesser numbers due to ringworm and syphilis, and 2 cases from X-rays. '^Vomen seemed to be more affected by loss of hair, in the relative proportion of 54 to 46, but possibly they consult physicians more freely on this account than do men. ALOPECIA (SCHAMBERG). 547 The author finds that heredity, dan- druff, systemic depression, fever, opera- tions and maltreatment of the scalp have been connected in the patients' minds with the fall of hair and, accord- ing to his figures, hereditary taint ex- ists in 30 per cent, while dandruff was present in 443 patients, a percentage of more than 19. Systemic depression was recorded in 120 cases, fever in 63, and maltreatment was evident in 277 cases, or nearly half of the whole num- ber. Most patients were unable to re- member the date of beginning alopecia, but it seems, from all the accurate data that could be obtained, that in the clinically uncomplicated loss of hair, it began before 30 in 84 per cent, of the males. In females it appeared at this early age in a much less percentage and seemed to be of later development. Dandruff appeared also earlier in men than in women, being about twice as frequent between the ages of 16 and 25. C. J. White (Jour. Amer. Med. Assoc, Sept: 24, 1910). ETIOLOGY AND PATHOLOGY. — Dandruff is generally regarded as the most potent cause of baldness. It is a plausible and attractive theory to attribute the process to microbic invasion. Sabouraud has brought forth strong evidence to show that his microbacillus is intimately asso- ciated with, if not the cause of, oily seborrhea. He likewise regards this organism as the cause of baldness. The microbacillus, according to him, enters the mouth of the hair follicle, multiplies, and forms a thin microbic lamina, which separates the hair shaft from the follicular wall. Epithelial irritation causes the encysting of the bacilli in a plug or cocoon. Then follows increased sebaceous flow, hypertrophy of the sebaceous gland, and progressive atrophy of the hair papillae. Sabouraud recognizes other causes which render the soil favor- able, such as city life, insufficient exercise, excessive meat diet, gout, heredity, etc. If baldness has a mi- crobic origin, Sabouraud is certainly correct in regarding the above causes — causes which are operative in the busy life of great cities — as of vast impor- tance. Premature baldness is rare or absent among savages and is less com- mon in country than in city districts. Many other factors have been in- voked as causes of baldness, such as Alopecia from a cured tinea favosa. {Schamberg . ) the too frequent wetting of the hair, the wearing of stiff* hats which con- strict the temporal arteries, etc. It is also stated that brain workers are particularly subject to premature alo- pecia ; this is probably more the result of sedentary life than of intellectual activity. Alopecia areata is often caused by traumatisms of the head. The exist- ence of anatomical and functional lesions of the central nervous system must be admitted, the state of central irritation -giving rise to peripheral 548 ALOPECIA (SCHAMBERG). trophic disturbances, which manifest themselves bj' the appearance of hy- peralgesic zones. Possibly, vascular lesions analogous with arteriosclerosis are the cause of the falling out of the hair. At anjf rate, the nervous lesion is the predominant etiological factor. Psychic traumatism, especially fright, has an identical effect. Weichselmann (Deut. med. Woch., Nov. 12, 1908). Alopecia of dental origin often fol- lows a painful attack of trigeminal neuralgia caused by the teeth (18 out of 25 cases). This attack may pre- cede the depilation by two or three months, but more commonly it occurs in the preceding month. It occurs on the same side as the trigeminal attack, more frequently on the left side be- cause dental lesions are more common on the left side. It appears by pref- erence in certain predisposed zones, as if there was a relation between the seat of the dental irritation and the seat of the initial area of alopecia. Thus, in 16 cases of trouble with the lower wisdom tooth the author found alopecia localized on the same side of the nucha in 14. It follows alveolar and gingival irritation rather than den- tal irritation proper. Thus, in 25 cases of dental alopecia the author traced the cause in 3 cases to inflammation of the dental pulp, in the remaining 22 to troubles outside the teeth. These irri- tations seem to act differently upon the trigeminus. It is accompanied by cer- tain phenomena, such as hyperesthesia, erythrosis, hyperthermia, adenopathy, lymphangeitis, and edema, grouped by Jacquet under the name of the dental syndrome. The areas are generally small in size and few in number. The prognosis is good. The cure is rapid and often immediate after dental in- tervention alone. Rousseau-Decelle (Presse med., Feb. 6, 1909). Many cases of hereditary syphilis show no sign beyond defects of den- tition— defects which, in spite of the now 25-years old teaching of Four- nier, are not yet, he says, sufficiently well known. The writer thinks it hardly conceivable that the teeth in these cases can have suffered with- out some imprint of the disease upon the viscera, nervous system, or bony structures. Such imprint does occur, and it renders the offspring of syphilitic parents more predisposed to attacks from other diseases, such as eczema, psoriasis, and alopecia areata, as regards the skin, and to tuberculosis, enteritis, and probably other internal diseases. Sabouraud (Presse Med., Mar. 22; May 17, 1917). PROGNOSIS. — Alopecia sebor- rhoeica gradually progresses, unless checked by treatment, to a denudation of the vertex leaving a fringe of hair in the temporal and occipital regions. Appropriate treatment, particularly if instituted earlv, will sometimes check the hair loss and lead perhaps to some regrowth. If systemic conditions are present which render the scalp a favor- able nidus, the outlook is more un- favorable. • TREATMENT. — The treatment mu.st be directed toward the existing seborrheic process. The measures em- ployed relate both to general and local treatment. Outdoor life, exposure of the scalp to sunlight, the restricted use of meats (Sabouraud says bald- ness is less common in vegetarians), the avoidance of excesses of all kinds, are to be recommended. Such tonics as iron, strychnine, phosphorus, arsenic, and codliver oil may be given with advantage. Local treatment is of great impor- tance, particularly when dandruff is present. It consists of the proper cleansing of the scalp and the stimula- tion of the sebaceous glands to healthy action. The tincture of green soap makes an admirable shampoo for the removal of epithelial and sebaceous debris. This may be advantageously followed by such a hair-wash as : — ALOPECIA (SCHAMBERG). 549 B Resorcinolis 3ij (8 Gm.)- Acidi acetici ... f5j-f3ij (4-8 c.c.)- 01. ricini f3ss-f3j (2-4 c.c). AlcohoUs,q.s.Z(\ ilx] (180 c.c). 01. bergamott... tti.x1 (2.4 c.c). When greater stimulation is desired, the following lotion may be used : — B Hydrarg. chlor. corros gr. viij (0.5 Gm.). BetanaphthoUs . gr. xxv (1.6 Gm.). Glyccrini fSj (4 c.c). Alcoholis _. f3iv (120 c.c). Aquce cologni- ensis fSss (15 c.c). Aqua fSiiss (75 c.c). Sig. : Hair-wash ; part the hair and apply with a small sponge. Another lotion frequently prescribed where stimulation is desired is as follows : — IJ Tinct. canthar- idis f 3vj (24 c.c.) . Tinct. capsici, Old ricini aa •ni,xxx-f3j (2-4 c.c). Spts. myrcia (bay rum), q. s. ad f5vj (180 c.c). It is a good plan in many cases to use an ointment in conjunction with hair lotions. The lotion may be used each day, and the pomade applied once or twice a week. The latter should be rubbed in in very small quantities, so as to avoid disagreeable greasing of the hair. When ointments are used con- jointly with w^ashes, the glycerin or oil in the lotion may sometimes be ad- vantageously omitted. Sulphur is the most useful agent for scalp pomades when any seborrhea is present. The following ointment gives most satisfac- tory results : — IJ Sttlph. prcecip 5j (4 Gm.). Adipis Sj (31 Gm.). 01. bergamott TTi.xl (2.4 c.c). Daily digital massage of the scalp is distinctly useful, as is also the vig- orous use of the hairbrush to produce hyperemia of the scalp. Successful treatment depends upon the promptness with which one first notices that the hair is beginning to fall. Healthy hairs do not come out, and if hairs are found on the pillow. on the clothing, or in the hairbrush, the indication is given for beginning the treatment. One of the most important yet very generally neglected, prophylac- tic measures consists in frequent ablu- tion of the head, a measure that is still considered injurious by many people. On the contrary, frequent shampooing and rubbing of the head is the best preventive of baldness. Another feature on which the author lays much stress is the necessity for cleanliness in all utensils used in the barber shop or in private. Actual baldness cannot be cured, but a great deal can be done to prevent its onset by properly treating the tendency to falling of the hair. A course of treatment is outlined, of which the fol- lowing are the most important features : Daily shampooing with soap and hot water, followed by drying and the ap- plication of a 1:1000 solution of bi- chloride of mercury. This is allowed to evaporate, and the scalp is then rubbed with a 1 : 400 solution of thymol or naphthol in alcohol. Fi- nally, an ointment is applied contain- ing 1 part of salicylic acid, 2 of tinc- ture of benzoin, and 50 of vaselin. In obstinate cases the treatment is be- gun by the application of tar liniment, which is removed ten minutes later with the soap. Lassar (Deut. med. Woch., July 5, 1906). The most satisfactory lubricant is cocoanut oil. It keeps the hair soft and silky and does not mat the hair or plaster it down. A good shampoo about once a month suffices. The wire brush keeps the scalp pretty free from dirt and dandruff. By its gentle and not disagreeable friction of the scalp, it promotes the circula- tion and thus brings nourishment to the hair-bulbs, and gives vigor to the growing hair. S. Hendrickson (Jour. Amer. Med. Assoc, Sept. 2, 1911). The writer considers local treat- ment of paramount importance, and the first part is the same for all forms of seborrhea. It is necessary first of all to remove from the scalp the scurf or any greasy scales that 550 ALOPECIA (SCHAMBERG). may be present, as they tend to block thoroughly done, for 20 or 30 min- the mouths of the hair follicles and utes at a time. The masseur should provide a favorable soil for bacterial use an emollient cream, such as: growth. During the first month of j^ ^^^^ ^,^^ _^^ ~^. (24 Qm.). treatment the head should be fre- p^^^.^^^- ^^. (150 Gm.). quently washed and anomted daily Aquce rosce . . . sHss (75 Gm.). with an antiseptic omtment. The Sodii boratis . gr. xxxx] (2A Gm.). head should be shampooed every eve- Sulthuris gree- ning with a spirit soap lotion and ^.^.^^,. 3^.^^ (28 Gm.). then, after the hair has been thor- ,, . I 1 J • 1 .u r 11 • * 4. M. et ft. crcmor. oughly dried, the following ointment is rubbed carefully into the entire Deep brushing with a long bristle surface of the scalp: brush for a few minutes night and I^ Acidi salicylid. gr. X (0.6S Gm.). morning is also advised, and elec- Suit'lmris 'pritati gr. XXX (2 Gm.). their advocates. Olciroscc mij (0.13 Gm.). Pilocarpine is the only drug that Adipis bcnzo- appears to exert a specific action. atis 5J (^0 Gm.). IJ Pilocarpiucc Misce. Ft. ungucntum. hydrochlo- Drugs that should never be used '"'''' S''- ^-^ (^-^ G'"-)- when the hair is light or gray are: ^^wc colomcn- _ Resorcin, beta naphthol, empyro- -^'-^ 5'^' (1^ Gm.). form, oil of cade, ichthyol, thiol, and ^^"^ '■^■^'^' tannic acid. Freshwater (Pract., Oct., Akohohs ah- \q\%\ soluti ....aajij (60 Gm.). rr^i - -.1 1 • 1 ii 1 M. Sig. : To be well rubbed in The trequency with which the scalp ■ , , ,- ^ t , . * night and mornnig. G. T. Jackson should be washed depends entirely upon ^^^ McMurtry (Med. Fortnightly, the degree of oiliness of the scalp and ]May 25, 1914). hair. A greasy scalp requires more fre- R^p^^t of 3 years' experience with quent cleansing than a dry one. In a an ultraviolet ray quartz lamp utiliz- general way it may be said that the ing 3^j amperes on a 220 direct cur- scalp should be washed about once in rent. Practically all forms of alope- two or three weeks. If the skin is very ^[^ ^^.^P°"^ *° '^^,^^^" alopecia senilis , . , 11,1, showing favorable results and alo- dry afterward, a pomade should be ^^^-^ ^^^^^^ ^„j trichophytina alwavs employed. Soaps containing sulphur responding rapidly. The distance and tar are useful. Some of the Ger- from lamp to skin is 10 inches, and man superfatted soaps, especially one the initial time of exposure 15 min- containing sulphur, salicylic acid, and "^^^ '" ^^""''^'^ ^"^ 20 to 25 minutes , , 1- -1 1 f 1" brunettes and gray persons. The resorcin, are particularly eligible tor ^ ,, u- * *u 1 *u ' t- J b younger the subject, the less the ex- the purpose. posure. A given area can be treated The drugs most successful in treat- but once a week, though with due ing loss of hair arc euresol, bichloride local protection other parts can be of mercury, captol and chloral hy- treated on the same or following drate. Temporarily one maj^ expect days. The eyes are protected by good or very good response in 48 colored spectacles, and other exposed per cent, of men and in 56 per cent. parts by zinc oxide plaster or 2 layers of women. C. J. White (Jour. Amer. of towels. Hair that might obstruct Med. Assoc, Sept. 24, 1910). the rays must be held away from the In premature baldness, massage of area to be treated, a bathing cap with the scalp should be frequently and appropriate windows being conven- ALOPECIA AREATA (SCITAMBERG). 551 fent. In recent cases a single treat- ment at times yields a cosmetic cure; in other patients a dozen exposures are required for satisfactory changes. DiefiFenbach (Amer. Jour. Electro- therap. and Radiol., Sept., 1917). In 25 cases observed by the writer, alopecia usually occurred 2 or 3 months after the onset of influenza, though occasionally during convales- cence. It v^^as generally of the diffuse type, although in 1 hospital case and 1 private case the lesions were patchy. In 21 cases the patients were females, but all were under 36 years of age. The aim should be to promote a healthy circulation of the scalp by massage with the head lowered; by avoidance of obstruction to the main vessels of supply to the scalp by pad- ding the hat band, and by stimulating lotions. Ayres (Boston Med. and Surg. Jour., Apr. 24, 1919). Jay F. Schamberg, Philadelphia. ALOPECIA AREATA.— Alope- cia circumscripta; area celsi. DEFINITION.— Alopecia areata is a disease of the hairy system char- acterized by the more or less sudden occurrence of round or oval circum- scribed bald patches, in rare cases coalescing and producing total bald- ness. SYMPTOMS. — The disease is usually limited to the scalp. The patches are circumscribed and round, and vary in size from a coin to the palm of the hand. The skin is smooth, soft, of a dead-white color, and totally devoid of hair. Occasion- ally the patches are pinkish as a result of slight hyperemia. The fol- licular openings are contracted and less prominent than in the healthy scalp. To the feel the skin is thin, soft, and pliable. In the beginning, the patches are level or slightly ele- vated, while later they are sometimes slightly depressed. The course of the disease is ex- tremely variable. In some cases the bald patches develop suddenly in the course of a few hours. In other cases, the hair loss is gradual, extend- ing over a period of a few da3'S or weeks. The areas then spread by peripheral extension until they reach Alopecia totalis following: an ordinary alopecia areata. {Schamberg.) a certain size, when they remain sta- tionary. In some cases the entire scalp becomes denuded of hair, giving to the patient a most grotesque appear- ance. In extensive cases it is by no means rare for the eyebrows and eye- lashes to be lost. In men the bearded region of the face may be involved, either alone or in conjunction with the scalp. The duration of the disease varies 552 ALOPECIA AREATA (SCHAMBERG). greatly. Recovery seldom occurs in less than a few months, while many cases last several years. The disease may occur at any period of life. In young individuals the hair usually returns sooner or later. In adults, the baldness may persist and prove refractory to all treatment. When regrowth occurs, the patch is first covered by fine, downy, whitish Alopecia areata. Schamberg . hairs which are either shed or later converted into coarse and pigmented hairs. Not infrequently the hair grows in and the patient thinks he is on the road to recovery, only to have his hopes shattered by the hair falling out again. As a rule, there are no sub-i jective symptoms to be observed in such cases. Alopecia areata occurs with similar frequency in the two sexes. It is more common in youth and early adult life than in other age periods. Crocker states that, of 506 hospital cases, 214 were under 15 years of age, and 214 occurred in persons between the age of 15 and 35. ETIOLOGY.— There are two dis- tinct theories of the causation of alopecia areata. One school insists that the disease is parasitic, and cites occurrences of epidemics in institu- tions as proof of this view. Epi- demics have been observed chiefly in France and Germany : Cowen and Putnam have also published the details of an outbreak in an institution in this country. The cause of alopecia areata is not an infection, but some neurotrophic influence. Division of the second cra- nial nerve experimentally causes it; besides, thallium acetate applications cause neurotrophic affections of the entire body. And with atrophy of the fibers of the sympathetic nerves in certain regions alopecia results, especially when the trigeminus is affected. From his observations the writer believes alopecia areata al- ways to be neurotrophic in character. E. Richter (Berl. klin. Woch., Dec. 29, 1902). Alopecia areata is trophoneurotic in origin, as first urged by Jacquet, who noted some close relation be- tween alopecia and dental neuralgia. His investigations show that neural- gia occurs before, with, or after the alopecia, in almost all cases. This dental theory of the origin of alo- pecia is confirmed by a case-history which the writer quotes, a child in whom the condition disappeared after the affected gum had been cauterized. F. Tremolieres (Presse med., June 14, 1902). Recalling Jacquet's theory that baldness is of nervous origin, and is connected with skin diseases, dental troubles, and crises of gastrointes- tinal and other origin, the writer re- fers to a case in which the cure of a fistula in ano, complicated with en- tire loss of hair, was succeeded by ALOPECIA AREATA (SCHAMBERG). 553 complete restoration of eyelids, eye- brows, and hair of the scalp. Eyraud (Presse med., Mar. 30, 1904). There exists a more or less inti- mate and obvious relationship be- tween genital disturbances and this disorder. In the female sex there is a form of alopecia that follows the menopause and even a prolonged sup- pression of the menses. Such alo- pecia may be either mild or severe. This disease may also follow oophor- ectomy, and here again the prognosis is variable. In less frequent instances alopecia appears, usually in a mild form, in the course of several con- secutive pregnancies. R. Sabouraud (Annales de dermat. et de svphil., Feb., 1913). Instance in an Italian boy, 5 years old, of ringworm of the scalp and alopecia areata appearing simultane- ously in the same location. He deemed it of some interest on ac- count of its possible bearing on the cause of some of the epidemics of alo- pecia areata occasionally reported. J. E. Lane (Boston Med. and Surg. Jour., Jan. 11, 1917). Illustrations of the teeth of piersons with alopecia areata. Some initial teratologic disturbance is responsible for the tendency for the hair to fall out, and for the defective teeth and defective growth of teeth and nails. Inherited syphilis is sometimes but not always responsible. Sabouraud (Presse Med., Aug. 23, 1917). On the other hand, there is irrefu- table clinical evidence of the neuro- pathic origin of cases of alopecia areata. Nervous shock, such as fright, prolonged anxiety, etc., and traumatism to the scalp have been directly followed by areate loss of hair. [I recently saw a boy admitted to the Polyclinic Hospital for the fracture of the skull who developed alopecia areata be- fore leaving the institution. Max Joseph has produced the disease in cats by ex- cision of the second cervical ganglion. J. F. S.] It would, therefore, appear that there are two varieties of alopecia areata, the one parasitic and the other trophoneurotic. In the epidemic ob- served by Bowen and Putnam, the patches were not identical with those commonly observed, but were smaller and more irregular in shape. Some of the English dermatologists are of the opinion that alopecia areata is prone to occur in those who have at some previous period suffered from ringworm of the scalp. Stimulating and antiparasitic reme- dies give the best chance of success in this affection, and in early cases there is a fair prospect of arresting the disease. The hair obtains its nutrition from the papilla, and the difficulty of reaching the deeper parts of the hair-follicle by external application must be borne in mind. The best remedies are probably those which keep the skin of the patch in a state of slight permanent irrigation, and this object may be obtained by the daily application of moderately strong irritants, such as tincture of iodine, lactic acid, acetic acid, chry- sarobin, sulphur and mercurial oint- ments. The author has found (1) the B. P. unguentimi hydrargyri iodidi rubri (diluted from 4 to 2 per cent.); (2) the unguentum hydrargyri oxidl rubri, r/ith acetum cantharidis, 3j to 5j (4 to 30 Gm.). and (3) equal parts of sodium chloride and petro- latum— used for the treatment of ringworm — serviceable for their anti- septic and stimulating properties. S. E. Dove (Clin. Jour., Jan. 21, 1914). The great French dermatologist, Sabouraud, regards his microbacillus as the probable cause of alopecia areata, though the influence of syph- ilis is not overlooked by him. In a review of current theories — the parasitic, the neurotrophic, and the reflex irritation theory of Jacquet — the writer dismisses them all. In some families it is hereditary. It oc- curs not infrequently in connection 354 ALOTECIA AREATA (SCHAMBERG). with vitiligo and exophthalmic goiter. It is common in women at or about the menopause. Apart from these groups a large number of cases, at least in childhood and adolescence, are due to syphilis inherited in a lar- val form, a view fortified by excellent results obtained with mercurial treat- ment. R. Sabouraud (Ann. de Derm, et de Syph., Ser. 6, i, 177, 1920). PATHOLOGY. — Both Giovanni and Robinson found evidences of in- flammatory disturbances, chiefly in 5-ail)papillary layer. Perivascular cell infiltration was observed in both early and late lesions. Subsequently atrophic changes take place with destruction of the hair papillae. The characteristic hair of alopecia areata has the shape of an exclamation point. The upper part is pigmented and normal, while the lower portion is atrophied and without pigment. Sabouraud describes an ampullar swell- ing {the pcladic utricle) filled with the microbacillus in the upper third of the hair follicle. Alopecia Areata. 1. Rapid onset. 2. Patches are : — (o) Totally devoid of hair. (&) Pale or whitish in color, (f) Smooth or soft, (rf) Follicles contracted. 3. Absence of fungus. 4. Common in adolescence and adult life. The baldness of early syphilis may bear some resemblance to alopecia areata. Apart from the presence of other evidences of the disease, the patches are moth-eaten in appearance and not sharply circvnhscribed. The surrounding hair and scalp are luster- less and dirty, whereas in alopecia are- ata they are perfectly normal. PROGNOSIS.— In children recov- ery usually takes place. In young adults the prognosis is usually favor- able, while in advanced adults it is un- favorable. The longer the disease has persisted, the more unfavorable is the prognosis. The duration of the disease is uncertain and relapses are not un- common. TREATMENT.— The internal treat- ment consists of the use of such tonics as iron, strychnine, quinine, codliver oil, phosphorus, and arsenic. Duhring considers arsenic to be "especially ser- viceable." The local treatment has for its pur- pose the stimulation and rubefaction of the scalp with the object of increasing the blood-supply to the follicles. Many cases terminate in spontaneous recov- ery, and conservative judgment is de- sirable in interpreting the value of remedies employed. Among the many medicaments which have been advised are alcohol, cantharides, capsicum, the essential oils, turpentine, carbolic acid, trikresol, ammonia, sulphur. Ringworm. 1. Slow, insidious onset. 2. Patches are : — (a) Covered with broken-ofF stumps. (b) More or less reddened. (c) Rough and scaly. {d) Follicles prominent ; "goose-flesh" appearance. 3. Trichophyton fungus present. 4. Occurs almost exclusively in childhood. iodine, mercury, chrysarobin, beta- naphthol, etc. The following lotion will be found of value : — IJ Tinct. cantharides, Tiuct. capsici, oi each fliss (6.00 c.c). 01. ricim f^ij (8.00 c.c). Aquce cologniensis . foj (30.00 c.c). Sig. : Brush in vigorously each day. Instead of lotions, ointments such as the following may be employed: — ALOPECIA AREATA (SCHAMBERG). 555 B Bctanaphtholis 5j (4.00 Gm.). Vasclini 5J (31.00Gm.). 01. bcrgainot ttlxI (2.46c.c.). Sig. : Rub in twice a day. An efficient treatment consists in the swabbing of the bald areas once or twice a- week with IJ Phcnolis, AlcohoJis. of each f5ss (15.00 c.c.)- Or, 50 per cent, trikresol may be employed. Within recent years I have em- ployed a chrysarobin ointment which has g-iven me more uniformly good results than anj^ other topical appli- cation : — B Chrysaro- biiii gr. x-xxv (0.65-1.62 Gm.). Lajwlini .... 5j (4.00 Gm.). Adipis bcnzo- inati 5vij (27.21 Gm.). M. Rub in in small quantitJ^ Protect the eyes from contact with ointment. Case of a young girl in which there was a circular patch three inches in diameter on the scalp at the side of the occiput, hairless, smooth, and shining. The treatment consisted in painting it with a 30 per cent, solu- tion of formaldehyde. This was done every daj- for the first week or two, until signs of inflammatory reaction appeared. The treatment was then suspended, and a sedative ointment applied. When the inflammation sub- sided the formaldehjde was again continued, stopping the application as soon as inflammatory trouble ap- peared. This routine of treatinent was persevered in for about six or nine months. About this time a growth of hair made its appearance, continued to grow, and in every way corresponded with the surrounding hair. One year after cessation of treatment the growth of hair was continuing in a perfectly normal way. J. J. Mclnerny (Brit. Med. Jour., Jan. 25, 1908). The writer deems it a great mis- take to treat the patch of alopecia alone; the aim should be especially to prevent the development of new patches. Another error is to wait to see whether the alopecia will subside; it is better to treat it from the first as if it were going to be a grave form. He advises to brush the en- tire scalp with a hard toothbrush dipped in a tonic and irritant mix- ture. His formula for this is: cologne water, 300 c.c. (10 ounces); glacial acetic acid, 10 Gm. (2^i> drams), and commercial solution of formaldehyde, 1 Gm. (15 grains). A lotion of 30 Gm. (1 ounce) of Hoffmann's fluid with 1 Gm. (15 grains) of glacial acetic acid is applied to the patch itself and its vicinity. In case the course of the alopecia seems threat- ening rapid extension, the small hairs broken off 3 or 4 mm. above the skin, he resorts to a cade oil salve. Men rub it in every evening and wash it out with soap in the morning; women three times a week with a weekly soap shampoo. The general health improves under mercurial treatment, as well as the alopecia ; the writer's success in this line has been so striking that he advocates mercurial treatment for young people with poor health or vague disturbances even if the idea of syphilis seems preposterous. When the alopecia develops at the meno- pause, ovarian treatment may aid, but spontaneous recurrence of hair is of- ten observed. R. Sabouraud (Presse med., Dec. 4, 1920). The faradic current applied with a wire brush electrode is often useful, as is likewise the use of high-frequency currents. In obstinate cases blister- ing of the affected areas may be re- sorted to. PHOTOTHERAPY.— Alany writ- ers, including Finsen, Hyde, Mont- gomery, Kromeyer, and others, have testified to the value of actinic light rays in this disease. It is admitted that many cases in which light is used might have recovered spontaneously. Kromeyer's results, however, in cases 556 ALUM (SAJOUS). of extensive and even total alopecia of years' standing indicate that light therapy is one of the most useful measures in the treatment of this disease. The iron arc or carbon arc may be employed. The ordinary London Hospital type of lamp suffices for this purpose and permits of the exposure of a surface area of the size of a silver dollar. Reaction varying in degree from an erythema to the formation of a blister results at the end of some hours. The same area can be again treated after the expiration of two or three weeks. Severe case of alopecia areata, re- bellious alike to applications of mer- cury bichloride, pilocarpine, croton oil, etc., as well as to the use of a constricting band and to internal medication, in which exposures of the affected areas to the ultraviolet rays, by means of Kromeyer's lamp, gave good results. These rays induce pro- nounced and prolonged cutaneous hyperemia. They are both more ac- tive and safer than the X-rays. R. Horand (Lyon med., Aug. 18, 1912). The ultraviolet rays have given ex- cellent results in the writer's hands in cases of alopecia areata and other dermatoses. A. Fischkin (Ills. Med. Jour., Alay, 1916). The quartz lamps (Kromayer and Alpine) are cleanly and convenient agents for the treatment of alopecia areata. The results in 50 cases, though not brilliant, were at least satisfactory. More than half of the patients were followed to complete recovery, while in 78 per cent, of the cases the new hair had at least begun to grow. Fox (Med. Rec, Nov. 27, 1920). J.\Y F. SCHAMRERG, Philadelphia. ALSOL. See Aluminum : Alu- minum ACETOTARTR.VTE. ALUM {Aliimen). — The alum used in medicine is, chemically, the double sulphate of aluminum and potassium [A1K(S04)2+ I2H2O]. It occurs in large, octahedral, translucent crys- tals, or as a colorless powder, odor- less, but with a sweetish, strongly as- tringent taste. When left in an open bottle, the salt becomes whitish on the surface, owing to the absorption of ammonia from the air. Dried, "burnt," or exsiccated alum {Alnmen Exsicca- tum), i.e., alum from which the water of crystallization has been driven out by heating, occurs as a white, granu- lar, strongly hygroscopic powder. DOSE. — The dose of alum for in- ternal use (rarely employed) is 5 to 30 grains (0.03 to 2.0 Gm.) ; the aver- age dose is 71/0 grains (0.5 Gm.). To secure an emetic effect, 1 to 2 drams (4 to 8 Gm.) must be given. MODES OF ADMINISTRA- TION.—Alum is soluble in 9 parts of cold water (the saturated solution thus containing, roughly, 10 per cent.), and in 0.3 parts of boiling water. It is completely insoluble in alcohol, but dis- solves readily in warm glycerin. Dried alum, possessing greater concentration than the crystalline form, requires more water for dissolution — 17 parts of cold and 1.4 parts of boiling water. When exhibited for other purposes than as an emetic, alum is best given in a fla- vored syrup, e.g., syrup of orange peel. When it is used to secure eiuesis, a siTiall amount of simple syrup may be employed as vehicle. The subsequent ingestion of warm water augments its emetic effect. For astringent gargles, sprays, anhydrotic lotions, and rectal or vaginal injections, solutions contain- ing 21/0 to 20 grains (0.15 to 1.2 Gm.) of alum to the ounce (30 c.c.) of water should be prescribed. When an astrin ALUM (SAJOUS). 557 gent eye-wash is desired, 2 or 3 grains (0.12 to 0.20 Gm.) of alum to the ounce of water may be used. The "alum curd," made by adding to a pint (473 c.c.) of milk 2 drams (8 Gm. ) of alum, boiling the mixture, and straining off the curd, is also a useful preparation for this purpose. Dried alum, being anhydrous, is especially adapted for use as a dusting powder, for insuffla- tion, and in ointments. It is applied to superficial growths as an escharotic. A glycerite of alum is official in the Brit- ish Pharmacopoeia. INCOMPATIBLES.— The salts of aluminum, including alum, are incom- patible with the alkalies and carbonates of the alkali metals ; with the tartrates ; with tannic acid, and with salts of iron, mercury, and lead. CONTRAINDICATIONS.— In in- dividuals subject to bronchial irritation, the long-continued use of alum is inad- visable, in view of the exciting effect it exerts on these structures. PHYSIOLOGICAL ACTION.— When applied externally alum causes hardening of the skin, or, if used in concentrated solution, exerts a slight caustic effect. Whenever it is brought in contact with albumin, as occurs when it is applied to a denuded area, the al- bumin is coagulated. The precipitate is soluble, however, if an excess of albu- min be present. The familiar astringent and antisep- tic effects of alum and other aluminum salts depend upon this coagulating property. Their power of penetrating into tissue-cells is, however, very limited according to Siem. Yet it is very effective when hemorrhage for in- stance is of capillary origin. Small doses of alum taken orally at first stimulate the flow of saliva, then reduce it through their astringent ef- fect. The buccal mucosa becomes whitish and shriveled, owing to coagu- lation of the albuminous constituents, and the enamel of the teeth is likely to crack in places. On reaching the stom- ach, the drug causes a decrease in the amount of gastric juice secreted, and coagulates the pepsin. A similar effect being exerted in the intestinal canal, constipation results. In larger doses, the emetic eft"ect of alum becomes man- ifest, and a purgative effect may also be noted, irritation succeeding the prelim- inary astringent effect. UNTOWARD EFFECTS AND POISONING.— The injurious eft'ect of alum on the teeth may be avoided (1) if care be taken to cleanse them well at once after employing an alum gargle or mouth-wash ; (2) by limiting the use of alum to applications of a strong solution or of the solid salt in all cases in which local astringent ef- fects will sufifice. The unfavorable ac- tion of alum when long employed by persons subject to bronchial irritation has already been referred to. The influence of alum in baking powders was studied bj- a Referee Board of Consulting Scientitic Ex- perts composed of R. H. Chittenden, A. E. Taylor, and J. H. Long, ap- pointed by the U. S. Department of Agriculture. The general conclusion reached was that alum baking pow- ders are no more harmful than any other baking powders, but that it is wise to be moderate in the use of foods that are leavened with baking powder. (Bulletin Xo. 103, Apr. 29, 1914). Large amounts of alum taken inter- nally cause nausea, vomiting, pain in the abdomen, and diarrhea, owing to the inflammation of the gastrointestinal mucosc-e produced through the cellular albumins. 558 ALUM (SAJOUS). Case in which, through gargling with a concentrated alum solution, a portion of the fluid was accidentally swallowed. This was followed by severe abdominal pains, vomiting of mucus and blood (39 times), and voiding of blood- stained urine. Recovery only after the lapse of thirteen days. Kramolin (Therap. Monatsh., 325, 1902). Alum baking powder.s and pastry to which akim has been added in order to whiten the product are possible sources of gastrointestinal irritation, though the amount of aluminum liberated, at least in the case of bread baked with alum powders, is often so slight as to be of doubtful imjportance. THERAPEUTIC USES. — As an Astringent. — This is the chief use of alum. Combined with it is an antisep- tic efifect, which is also of value. In all catarrhal and relaxed states of the mucous membranes, as well as in certain skin affections, alum is bene- ficial when locally applied. Aqueous solutions of from 5 to 20 grains to the ounce (1 to 4 per cent.) strength are chiefly employed ; stronger solutions in- duce undesirable secondary irritation. In catarrhal throat affections fluid preparations containing alum (1 to 5 per cent.) form a useful gargle or spray. Since alum is injurious to the teeth, the mouth should be washed out, preferably with some alkaline so- lution, after using this drug. A glycerite of alum (10 to 20 per cent, solution of alum in glycerin, the prep- aration of which is greatly facilitated by heating) is very efficacious when applied locally in subacute pharyn- gitis and laryngitis, especially where a tendency to edema of the tissues in- volved is present. For the relief of hoarseness or of tickling sensations in the throat, a mixture of equal parts of powdered alum and sugar, placed on the tongue and allowed slowly to dissolve, is productive of benefit (Bunnell). In acute coryza alum has been incorporated in snuff, to which it imparts astringency. The following preparation is suitable for use in the early stages of coryza: — IJ Alum 3 grs. (0.2 Gm.). Morphine sulphate . 2 grs. (0.13 Gm.). Cocaine hydrochlo- ride Igr. (0.065 Gm.). Camphor, Bismuth of each 2 drs. (7.77 Gm.). M. bene. Sig. : To be used as snuflf every two hours; a small quantity in each nostril. In follicular tonsillitis and diph- theria alum in pencil form may be applied to the involved surfaces with benefit. In conjunctivitis alum may also be used. A 0.5 per cent, solution may be used as a lotion, or the alum curd, made by the addition of powdered alum to milk oj white of egg until a curdy mass is formed, may be ap- plied to the eye every two hours. Similar applications prove effective in ecchymosis of the eyelid (black eye). In gonorrheal ophthalmia alum has also been used in a solution con- taining 6 grains of the salt in 1 ounce of water, applied four times daily. In granular conjunctivitis a crystal of alum may be drawn over the involved mucous surface after turning the lid (Bunnell). In salivation or ptyalism of mer- curial origin a 4 per cent, solution of alum may be employed for its astrin- gent action. In the treatment of night-sweats, or in sweating of the hands and feet (hyperidrosis), washing the skin sur- faces with a 0.5 per cent, solution of alum will markedly improve the con- dition. ALUM (SAJOUS). 559 In chilblains a 4 per cent, solution of alum has been applied with benefit. In gonorrhea and leucorrhea alum has been used as an astringent injec- tion or douche in ^o to 2 per cent, strength. In pruritus vulvae a 4 per cent, so- lution of the salt will not infrequently relieve the itching. In ingrowing toenail with granula- tions absorbent cotton soaked in a 6 per cent, solution of alum may be in- troduced under the edge of the nail. In chronic dysentery a 1 per cent, solution of alum is sometimes em- ployed as a rectal injection. As a styptic alum is likewise an effective agent. In epistaxis it will often act promptly. Pledgets of cotton should be dipped in a saturated solution of alum and packed in the bleeding cav- ity; they may be left in until all danger of recurrence has passed — generally about twelve hours. In minor degrees of hemorrhage the alum solution ma}^ be sprayed in, or pow^dered alum may be used as snufif or introduced by means of an insuf- flator. Similarly, in hemorrhage succeed- ing upon the extraction of teeth, the placing in the cavity of cotton dipped in a saturated solution, or the intro- duction of powdered alum, will often be effective in arresting the bleeding. In hemoptysis a fine spray of 5 per cent, alum solution is claimed to have been productive of benefit. In the intestinal hemorrhage of ty- phoid fever alum has been recom- mended by many clinicians, Whitla in particular. It is believed to do good in this condition through its antiseptic properties, as well as through its astringency. In uterine hemorrhage of all kinds alum is a useful styptic. It may be employed as an injection in the strength of 1 dram to the pint, or, as R. Beverly Cole recommended, an egg-shaped piece of alum may be inserted into the uterine cavity. Not only is the styptic effect produced, but the tissues of the uterus are stim- ulated and the organ is caused firmly to contract. As a Caustic. — Dried ("burnt") alum, which exerts an escharotic ef- fect, owing to the fact that in addi- tion to the inherent properties of alum it withdraws water from the tissues, ma)^ be applied to exuberant granulations, condylomata, chronic conjunctival inflammations, etc. Burnt alum may also be used as a dressing for sluggish ulcerations and as an application to swollen gums and in ulcerative stomatitis (Bun- nell). As an Emetic. — In doses of 1 or 2 drams alum has been used as an emetic, especially in the treatment of croup in children. A teaspoonful of the salt may be dissolved in 6 table- spoonfuls of a mixture of syrup and water, equal parts, and administered every fifteen minutes. This sometimes serves quickly to ar- rest an impending attack of croup, the astringent effect of the salt upon the mucosa of the throat contributing in the benefit by counteracting the local hyper- emia. As a Stimulant to Peristalsis. — In doses of % dram every four hours alum has been found to induce purga- tion. The large amount of watery fluid thrown out from the mucosse in the presence of alum apparently obviates its irritating influence on these mem- branes. In tympanites due to peri- 560 ALUMINUM (SAJOUS). toneal inflammation succeeding upon alidominal operations in cases suffer- ing from infective states of the ab- dominal viscera, the high rectal in- jection of an ounce of alum in a quart of water has been found effectively to excite contractions of the paretic gut. Case in which Epsom salt, calomel, soap and water, castor oil, glycerin, turpentine, and oxgall were success- ively used without avail. A solution of an ounce of powdered alum in a quart of warn water was injected into the rectum, and in ter minutes flatus escaped from the rectum. In an hour the enema was repeated successfully. The patient was practically convales- cent on the following day. Since this case, the author has used the alum enema in hundreds of cases, and always with good results. Sometimes it is necessary to repeat the injection be- fore it will act, and this can be done with safety an indefinite number of times. There is sometimes some pain, not severe, attending its use. Injected like any other enema, probably in no instance does it go above the sigmoid flexure. The throwing off by the bowel of a tubular cast is of no importance, as it is composed simply of mucus whose albuminous elements have been coagulated by the alum. The alum seems to have as specific an action in inducing intestinal peri- stalsis as has castor oil when taken into the stomach. It does not produce a serous exudation from the intestinal walls, and for that reason the author prefers it to Epsom salt when the stomach will retain it. During nine years in which alum enema was used, percentage of mortality in abdominal work has been a little less than one- half of what it was during the pre- ceding seven years. Hardon (Amer. Jour, of Obstet:, June, 1901). C. E. DE M. S.\JOUS AND L. T. DE M. S.\jous. Philadelphia. ALUMINUM {Aluminium). — A bluish-white, silvery metal, noted for its low specific gravity (2.7) and its unalterability on exposure to the air. The most important of the com- pounds of the metal aluminum em- ployed in medicine, viz., the double sulphate of aluminum and potassium, has already received separate consid- eration (v. Alum). Numerous other salts have been used, chiefly exter- nally, as astringents and antiseptics. Taken internally, the salts of alumi- num are, according to some observers, not all absorbed from the gastrointesti- nal tract, this accounting for the fact that no functional disturbances in the organism at large occur as a result of their ingestion. According to others, however, alum (and probably other salts) is absorbed, in extremely small amount, in the alimentar)^ canal, and is eliminated with the bile and urine. When administered experimentally to animals by subcutaneous injection, soluble salts of aluminum cause no symptoms at all until several days or even weeks later (Siem), when the metal is no longer present in the cir- culation. In mammals the symptoms appear in from three to five days, and are in many ways similar to those of subacute arsenic poisoning. The ani- mal shows loss of appetite, obstinate constipation, emaciation, and languor. Next there appears vomiting. Vol- untary movements, executed only upon coercion, are attended with trembling and twitching. Sometimes there is general tremor or convulsive twitching, and sometimes extreme weakness or partial paralysis of the posterior limbs. There is complete loss of sensibility to pain, though 'consciousness is retained. Finally, control of the tongue and the power ALUMINUM (SAJOUS). 561 of swallowing are completely lost, sa- liva dribbling from the mouth. The symptoms correspond precisely to those of human acute bulbar paraly- sis. Such phenomena never result from the oral use of aluminum salts, even where long continued (Soll- mann). Diarrhea and albuminuria appear before death. On post-mortem examination the gastrointestinal mu- cosae are found hyperemic and swol- len, and the kidneys and liver fre- quently show fatty degeneration, the former presenting, in addition, corti- cal hemorrhages. When aluminum vessels were first used for cooking some doubt existed as to their safety. Increasing experi- ence has shown that such objections do not exist. The writer observed that the largest amount of aluminum was detached when marmalade was made with oranges and lemons, but the amount recovered was so small that it would have been perfectly harmless even if the entire IV2 ounces of preserves had been eaten at one meal by a single individual. John Glaister (Editorial Therap. Gaz., Sept., 1913). When aluminum, in the form of aluminum lactate or sodium alumi- num lactate, is fed to rabbits, cats, or dogs for long periods of time, cer- tain distinct effects such as diarrhea, with, at autopsy, corrosion of the stomach, together with congestion, and a hemorrhagic condition of the intestinal mucosa result. Large doses caused numerous areas of intestinal hemorrhages and a few areas of ulceration, which were especially marked in the large intestine. Roth and Voegtlin (Jour. Pharm. and Ex- per. Therap., Feb., 1916). Following are some of the more important salts of aluminum em- ployed in medicine : — Aluminum Hydroxide {A\nm\)V Hydroxidum), Al(OH)3, made by precipitating a soluble salt of alumi- num with an alkali or alkaline car- bonate. It occurs as a light, amor- phous, colorless, tasteless powder, soluble in acids and alkalies. It is used as an astringent in inflamma- tory skin affections. Aluminum Sulphate {Alumini Sul- phas), AloC 504)3 + I8H2O, prepared from the hydroxide by dissolving it in dilute sulphuric acid. It occurs as a white, crystalline powder or in larger cr}' stals or pencils, and, like alum, has a s\veetish and astringent taste. It is freely soluble in water, and has been used for much the same pur- poses as alum itself, viz., as an astrin- gent, antiseptic, and caustic in the treatment of affections of the nose and throat, including enlarged tonsils and nasal polypi; of the uterus, includ- ing endometritis ; as a lotion for foul ulcers, and in vaginal conditions as- sociated with offensive discharges. The strength of the solutions used is the same as with alum. The following aluminum com- pounds are non-official : — Aluminum Acetate (basic), AI2O,- 4C2H3O2 + 4H2O. Obtained in solid form from its solutions by rapid dry- ing on glass at a low temperature, this salt occurs as a colorless, cr\^stal- line or amorphous powder wdiich is insoluble in w^ater. It is antiseptic and astringent, and has been used in- ternally in dysentery in doses of 5 to 10 grains (0.3 to 0.6 Gm.). An 8 per cent, solution of aluminum acetate is known as "liquor Burowii," which has been extensively used as an appli- cation in skin affections, and in sup- purating wounds. One to 3 per cent, solutions are useful as a mouth-wash, and are particularly effective in over- coming fetid breath. In a solution of 1—36 562 ALUMINUM (SAJOUS). 1 to 150 strength, this salt of aluminum may be used as an astringent enema in affections calling- for sucli a measure. Usefulness of aluminum acetate solu- tion emphasized. For certain surgical purposes this is one of the best anti- septic solutions, though it is unknown to most surgeons and practitioners. Burns may be treated with dressings wetted with a 1 per cent, solution of aluminum acetate. This solution, while antiseptic, is also non-toxic, non-irri- tant, and yet markedly astringent. It is not to be employed in surgical opera- tions, as it spoils steel instruments ; but as an antiseptic for moist fomentation of wounds that are infected or prob- ably unclean, or as a medicament for a bath in which to place an infected hand or foot for continuous irriga- tion, it is to be strongly recom- mended. The common strength is that of 1 dram of the liquor aluminii acetatis of the German Pharmaco- poeia (a 7,'4 per cent, solution) to 1 fluidounce of water. There is no danger of poisoning from it. By the employment of continuous irrigation by means of a bath of the 1 per cent, solution, pyogenically infected hands and feet, which but for the action of the solution would have called for amputation, have been saved. For dermatitis, whatever its cause; for suppurating open wounds, and for cutaneous erysipelas, much is to be said for the favorable results ob- tained. One objection that should be mentioned is that after three weeks of continuous irrigation of a member such as the hand the surface tissues may assume a ligneous hardness. M. F. Waterhouse (Hospital, Aug. 27, 1910). The w-riter observed 3 cases in which dressings with solution of aluminum acetate produced necrosis of the injured hand. The effect of the dressing was similar to the burns caused by phenic acid. Esau (Med. Klinik, July 14, 1912). Aluminum Acetotartrate (Alsol), prepared by mixing a 5 per cent, solu- tion of basic aluminum acetate with a 2 per cent, solution of tartaric acid and evaporating to dryness. It occurs in colorless crystals, or in whitish amorphous masses having a slightly acid, astringent taste. It dissolves slowly, but completely, in water, but is insoluble in alcohol and ether. This substance has an action sim- ilar to that of aluminum acetate, and is one of the best of the aluminum salts used in medicine. It has been employed largely, though not exclu- sively, in diseases of the respiratory passages. Thus in 0.05 to 2 per cent, solutions it has been used as a nasal 'douche. Mixed with 2 parts of pow- dered boric acid it may be used as a snuff. In tonsillitis a 1 per cent, so- lution of it makes a suitable gargle. Strong solutions {e.g., 50 per cent.) have been employed with advantage in the treatment of chilblains and skin diseases of various kinds — also in wounds as disinfectants. Eye af- fections, such as ophthalmia neona- torum, chronic types of conjunctivi- tis, etc., have also been treated with this salt. Solution of aluminum acetate is more efficacious than the commoner applications, iodine, ichthyol, lead and' opium, etc., in the treatment of local congestions such as boils, carbuncles, and especially in facial erysipelas. He has used it also with marked suc- cess in severe cellulitis and inflamma- tory rheumatism and declares it the best remedy for ivy poisoning. Sev- eral thicknesses of gauze are soaked with the solution and applied to the part, covered with rubber tissue or oiled silk, and a bandage applied. It need be renewed only once or twice in 24 hours. Liquor alumini acetatis of the National Dispensatorj' is the best solution, and is made up as fol- lows: Aluminum sulphate (X. S. P.), acetic acid (N. S. P.), of each, 300 ALUMINUM (SAJOUS). 563 Gm. (10 ounces); calcium carbonate (C. P.), 130 Gm. mi ounces'); dis- tilled water, 1000 c.c. (1 quart). Stansbury (Amer. Jour, of Surg., Feb., 1912). Aluminum Boroformate, prepared by saturating with freshly precipi- tated and "well-washed aluminum a solution of 2 parts of formic acid and 1 part of boric acid in 6 or 7 parts of water. It occurs in pearly scales, which are hygroscopic and dissolve completely, though slowly, in water. Its solution has a sweet, faintly astringent taste, and does not co- agulate solutions of albumin. ]\Iar- tenson in 1894 recommended this salt strongly for use as a gargle in the throat affections in children, prefer- ring it to all other preparations of aluminum, partly owing to its relatively pleasant taste. Aluminum Borotannate (CutaD, a product of the reaction of tannic acid with borax and aluminum sulphate. It is a brownish insoluble powder, which combines with tartaric acid to form Aluminum Borotannotartrate (soluble Cutal). This salt, in common with the other aluminum compounds, is anti- septic and astringent. It has been used chiefly in skin affections and is recommended particularly in weep- ing eczema and pruriginous affec- tions. The following formula may be emplo}ed : — B Aluiiiininn boro- tannate 1 dr. (4 Gm.). Olive oil 2y2 drs. (10 Gm.). Lanolin, .to make 10 drs. (40 Gm.). "\^4^en the flow of secretions has been arrested, the drug may be used with advantage as a dusting powder and astringent in the following mix- ture : — R Aluminum boro- tannate. Zinc oxide, PoTvdcrcd talc, of each ly. drs. (10 Gm.). In hemorrhoids Koppel has recom- mended the use of an ointment con- taining 10 per cent, of cutal, and in fissures of the hands of one formu- lated thus : — '^ Cutal M dr. (3 Gm.). Oil of sweet alm- onds, Lanolin ..of each 3}4 drs. (IS Gm.). Orange-flower water 2vS fl. drs. (10 Gm.). Aluminum borotannotartrate, or soluble cutal, has been used in tlie treatment of second-degree burns, as a 10 per cent, solution in glycerin in follicular throat affections, in catar- rhal metritis, in hemorrhoids, and in gonorrhea. Aluminum Borotartrate (Boral), a combination of aluminum, boric acid, and tartaric acid. It occurs as white crystals having a sweetish, astringent taste, and is freely soluble in water. It is useful in inflammatory diseases of the nose and nasopharynx, in ery- sipelas, and, in solution with tartaric acid, has given good results in gonor- rhea. It may be employed either alone in watery solution or in glycer- inated mixtures. Aluminum Carbonate, Alo(C03)2, occurring in chalky-white, easily pow- dered, tasteless masses. According to Gawalewski, it constitutes an ex- tremely mild styptic and astringent, and is hence better adapted than are burnt alum and other aluminum prep- arations in the treatment of various ocular affections, croup, diarrhea, hemoptysis, skin eruptions; and hy- peridrosis. 564 ALUMNOL. Aluminum Chloride, AUClc, + 12- H2O, a yellowish granular, crystal- line, hygroscopic powder, soluble in water, alcohol, and ether. It has been used internally in tabes in doses of IVo to 4 grains (0.1 to 0.25 Gm.), and externally as a disinfectant. Aluminum Phenolsulphonate (Sul- phocarbolate), Al2(C6H4HS04)6, a reddish powder with weak phenol-like odor and a strongly astringent taste, soluble ill water, alcohol, and glycerin. It has been recommended as a sub- stitute for iodoform in the treatment of superficial, circumscribed, suppu- rating lesions, and of cystitis. Aluminum Salicylate, Al(CoIl4- OHCOO);>, a reddish powder, insol- uble in water and alcohol, soluble in alkalies. Used as an antiseptic pow- der for insufflation in catarrhal states of the nasal and pharyngeal mucous membranes, and in ozena. Aluminum Silicate, AUSigOj), a white sul)stancc, insolul:)le in water and acids. It has been recently rec- ommended in the treatment of gastric hyperacidity and hyperesthesia. Investigations of the action of sili- cate of aluminum upon the gastric se- cretions and upon disease symptoms resulting from almormalities of secre- tion. Under the name ncutralon, this substance occurs as a fine, tasteless, odorless, and insoluble powder. Taken into the stomach it reacts with the excess of hydrochloric acid to form silicic acid and aluminum chlo- ride. The latter acts as a protective and astringent to the gastric mucosa in a manner similar to silver nitrate and bismuth, and has no toxic eflfect. In all cases of hyperacidity or hyper- secretion, whether of neurotic origin or due to organic disease or injurj-, the remedy was found to be very effective in reducing the acidity, re- lieving pain, and aiding digestion. Results especially good in persistent cases of hypersecretion with motor insufficiency. Gastric hyperesthesia associated with anemia and chlorosis favorably influenced in several in- stances. Excessive acidity in cases of gastric ulcer was also reduced. The drug was given in doses of ^ to 1 teaspoonful in 3 ounces of water, one-half to one hour before meals. No untoward symptoms. Rosenheim and Ehrmann (Deut. med. Woch,, Jan. 20, 1910). C. E. deM. Sajous AXD L. T. DE M. Sajous, Philadelphia. ALUMNOL, the aluminum salt of betanaphthol-disulphonic acid [AloCCio- H.-,OH(SO:{)2).'j1, is made by adding a solution of barium naphthol-disulphonate to one of aluminum sulphate, filtering oflf the precipitate of barium sulphate, and evaporating to dryness. It contains about 5 per cent, of aluminum, and occurs as a fine white or slightly reddish, non-hygro- scopic powder with a sweetish, astringent taste. It is readily soluble in cold water and in glycerin, slightly so in alcohol, and is insoluble in ether. On exposure to the air it becomes darker in color, by virtue of its reducing properties. MODE OF EMPLOYMENT.— Alum- nol is employed chiefly in solution, though also frequently as a dusting powder. As a mild astringent and antiseptic it is used in solutions of 0.5 to 5 per cent, strength. For caustic effects, a 10 or 20 per cent, solution may be employed. Where the action of several antiseptics at once is desired, alumnol may be used in com- bination with agents such as corrosive sublimate, resorcin, etc.; it is incompatible, however, with silver nitrate or other re- ducible salts, as well as with alkalies. THERAPEUTIC USES.— The almost unirritating and non-toxic qualities of alumnol in weak solutions render it avail- able as an astringent and antiseptic for the treatment of chronic catarrhal proc- esses, and also in sluggish ulcerations. In acute cases, however, it generally proves too irritating to be of value. It has been employed mainly in gynecology and gen- ALUMNOL. 565 itourinary surgery, and, to a less extent, in general surgery, laryngology, and derma- tology. In Yz to 1 per cent, solution alumnol was found useful by Heinze and Liebreich in gonorrheal endometritis and in colpitis not of gonorrheal origin. Kontz, employ- ing alumnol in a series of 16 gynecological cases, found that cervical catarrh and simple perimetritis j-ielded to its repeated use, and that gonorrheal vaginitis was readily cured by it. In endometritis ac- companied by adnexal lesions, however, pain was augmented, owing to the irrita- tion. This author employed a 3 per cent, solu- tion for lavage, a 10 per cent, solution in the treatment of endometritis and ero- sions, and powders and bougies of 20 per cent, strength. Marfan used 3 per cent, bougies of alumnol in vulvovaginitis. Intra-uterine injections of the iodide of alumnol have been recommended by Gram- matikati as a substitute for curettement of this organ. Though alumnol has been claimed to exert a peculiarly destructive action on gonococci, its use as an injection in gonorrhea in the male has not led to re- sults commensurate with earlj- expecta- tions. Casper employed it in 12 cases of acute gonorrhea, 20 chronic cases, 4 cases of gonorrheal epididymitis, 2 of post- gonorrheal adenitis, and 2 of soft chancre, administering intraurethral injections of 0.25 to 2.0 per cent, solutions; he did not find it superior to other drugs in general use. Samter confirmed these findings, though Chotzen claimed to have obtained good results. In the cases of soft chancre in Casper's series healing was promoted by the application of alumnol. Asch used a 10 to 20 per cent, solution for cauteriz- ing the lacunse and crypts at the urethral orifice. As a surgical antiseptic, alumnol is used in 0.5 to 3 per cent, solutions. In the dressing of wounds and in ulcerations, specific or non-specific, Eraud found it to produce no irritation or pain. As a desic- cant powder for wounds this author con- siders it efficacious. In nose and throat practice, alumnol has been found valuable in simple chronic and hypertrophic rhinitis, in ozena, in catarrhal and follicular tonsillitis, and in acute and chronic pharyngitis. It is used either in a 1 per cent, solution as a douche, in a water}' glycerin solution (1:5), to be ap- plied to the affected parts, or as a powder, mixed with Starch (10 to 20 per cent.), for insufflation. Stepanicz found that in acute laryngeal affections the roughness of voice generally disappeared after a single in- halation of a 1 per cent, solution. In chronic cases, insufflations of alumnol and starch (2 to 10 per cent.) also gave good results. Metzerott used alumnol with satisfaction not only in larj^ngitis, pharyn- gitis, tonsillitis, and peritonsillitis, but also in edema, syphilis, and tuberculosis of the larynx. In a case of symptomatic laryn- geal edema, probably of sj^philitic causa- tion, with a severe grade of stenosis, the administration of alumnol solutions in the form of injections and the steam spray made it possible to defer tracheotomy for six months. In the case of a singer troubled with subglottic laryngitis, with wave-like fluttering of the vocal cords, an alumnol spray gave early relief; also in one of chorditis nodosa (singer's nodules), strong solutions of the remedy proved beneficial. In otology alumnol has also been em- ployed. In suppurative otitis media Heath noticed, however, that it sometimes caused persistent burning sensations, and that it tended to unite with pus in the exter- nal meatus to form stone-like pellets, — a peculiarity condemning its use in this disorder. In dermatology alumnol has been found serviceable in powder form (12 to 25 per cent.), collodion (5 to 10 per cent.), and ointment (1, 5, and 12^ per cent.). It has proven effective in dermatitis, acute eczema of all sorts, and chronic eczema, but in sj^philis and the parasitic skin affections did not yield much benefit. In acne and acne rosacea as good results have been obtained with it as by most other methods of treatment. Chotzen found alumnol effi- cacious in acute and chronic inflammations of the skin and mucous membranes, in- cluding erysipelas, favus, lupus, soft chan- cre, and erosions. Eraud made the state- ment that alumnol appeared to be useful in certain varieties of pruritus, especially of the anus and scrotum. S. 566 ALYPIN. ALZHEIMER'S DISEASE. Ai(YPIN. — This is a white crystalline neutral powder, very soluble in water, which is not precipitated by alkaline fluids. Its properties are not impaired by boiling for 10 minutes. It was introduced as an anesthetic to replace cocaine. A 1 per cent, solution produced deep anesthesia of the rabbit's cornea in 50 or 60 seconds. The lethal dose in dogs and cats is about double that of cocaine. It is relatively non-toxic and is a pure local anesthetic. It has been used in a 2 per cent, watery solution. When dropped into the con- junctival sac there is a slight smarting. In about 70 seconds the conjunctiva to- gether with the cornea is insensitive to touch. A few seconds later the ocular conjunctiva may be seized with fixation forceps without the patient experiencing pain. There is usually some dilatation of the superficial vessels, but no dilatation of the pupil. There is no interference with accommodation; it does not affect the cor- neal epithelium. Alypin has been lauded by several ob- servers, according to Wolff Freudenthal (Med. Record, July 20, 1912), but others assert that the anesthesia produced is verj' weak. It may be used for removal of en- larged turbinated bodies, since it does not cause, as docs cocaine, a verj' marked con- traction of the hypertrophied turbinal tissues. Untoward Effects. — A. H. Miller (Jour. Amer. Med. Assoc, Jan. 17, 1914) reported 103 cases in which alypin had been used as a local analgesic. Of these 35 were minor surgical operations and 69 genito-urinary. In 100 of the cases analgesia was per- fectly satisfactory, in 2 the analgesic caused serious difficult)^ and in one in- stance death. In the last case tlie patient was an apparentlj- healthy adult, 39 years of age, who was about to undergo dilata- tion for stricture of the urethra. About 2 drams (8 Gm.) of a 10 per cent, solution were introduced into the urethra and bladder. Two minutes later the patient had a general convulsion, followed by a half-dozen during the next 10 minutes, with cessation of respiration and arrest of the pulse. Artificial respiration and stim- ulation were tried without avail. In a very similar case the patient was revived atter about 2 hours' work. In a third un- toward case about V/2 drams (6 Gm.) of a 10 per cent, solution was introduced into the urethra and bladder for dilatation of a stricture. In 3 minutes the patient be- came unconscious, and respiration became embarrassed, but tlie pulse remained good. Artificial respiration and inhalations of oxygen brought this patient around in about 10 minutes. The author considers Bremmermann's technique of depositing a tablet of alypin at the point of analgesic localization as far preferable to injecting an unmeasured quantity of the 10 per cent, solution into the urethra, at best a dangerous procedure. S. ALZHEIMER'S DISEASE.— Two cases of this rarely encountered mental disorder, both in men of 49, were reported by C. I. Lambert (Psychiatric Bull., Oct., 1916), both with a history of alcoholism. A most profound dementia developed slowlj- and insidiously in both. Inattention, indifference and absentmind- edness, declining efficiency, progressive impairment of memory, of retention, grasp and poverty of thought, followed by aim- less, restless, foolish behavior and increas- ing mental dilapidation which went on apace toward an apathetic dementia, in- capacity to comprehend, to talk, to walk; this was followed by a bedfast state in which the patient muttered and mumbled and fussed and fumbled, and pulled at his bedding, wet and soiled himself, chewed a little and gulped what was put in his mouth and vegetated for a time and died like a decerebrated animal. Among the more striking symptoms in these cases were the outstanding symptoms of ag- nosia, aphasia and apraxia. As a rule, in such cases, there is grad- ual development of severe dementia with signs of cerebral organic disease. With the dementia are focal phenomena causing aprasic, aphasia and asymbolic disorders. Alzheimer's disease is distinguishable from cerebral arteriosclerosis owing to the fact that apoplectiform attacks do not take part in the development of the high grade dementia and focal s^'mptoins. The morbid mental phenomena develop slowly and not paroxysmally, while the signs of arteriosclerosis throughout the system are generally absent. S AMAUROSIS (HANSELL). rO/ AMAUROSIS. -DEFINITION. — Amaurosis, formerly used to desig- nate partial or complete blindness, has become, since the common em- ployment of the ophthalmoscope, much more limited in its meaning and application. At present, imper- fect vision not due to errors of refraction or visible pathological changes may be classified under "amblyopia" ; complete blindness of one or both eyes and usually that form of blindness caused by disease of the nervous apparatus of sight, the retina, optic nerve, and cerebral centers under amaurosis. [Both words should be so used that they refer only to certain kinds of blindness which are to be described by a preceding adjective, and unless thus defined their meaning is vague and uncertain, carrying no suggestion of etiology or pathology. \A'hen the media of the eye are transparent, normal or abnor- mal conditions of the fundus are as easily diagnosed by the expert ophthalmologist as are diseases of the skin by the dermatologist ; therefore, except as a convenience or as a substitute for the word blindness, amaurosis might well be omitted from ocular vocabu- lary. Eyes blinded by disease of or trau- matism to the middle or anterior third are seldom described as amaurotic eyes. H. F. Hansell.] Amaurosis in Brain Disease, — Tumors or other organic changes in the brain by which the optic tract is directly compressed or the ventricular fluid is forced into the optic nerve sheaths will produce blindness. The process is a mechanical one. In the former the optic nerve fibers in the tracts are directly compressed and deprived of their function ; in the latter, the optic nerve is surrounded by fluid contained within a sac of only moderate distensibility. The gradually induced compression of the nerve induces arterial anemia and venous congestion of the nerve-head and retina, which is soon followed by serous and solid exudation into the distal extremity of the nerve. Finally the optic nerve fibers become atro- phied from stoppage of circulation and pressure of exudation. The loss of vision may commence in the pe- riphery of the field and advance by slow stages toward the center imtil finally the entire field is waped out ; or, as may be the case in apoplexy, a section of the field, one-half, one- quarter, or less, or the region about the fixation point and including it, is suddenly lost. Continuation or ex- tension of the brain lesion will be fol- low^ed by loss of the entire visual field. Amaurosis in Nephritis. — Disturb- ance of vision may be caused by hemorrhage or edema into the cere- bral centers, by pressure upon the chiasm or tracts, or by the action of the poison of uremia, by which the brain functions are held in abeyance. In the first and second it may afifect one or both eyes and be partial or complete. In the third it comes on rapidly, involves both eyes, and dis- appears in a few hours or in a day or two. There are no ophthalmoscopic changes visible in the retinal circula- tion or structural alterations in the nerve or retina. The blindness is strictly cerebral. In the early stages of hemorrhage or edema the eye- grounds are normal ; later they show the signs of intracranial pressure. In a man who died twelve hours after cerebral hemorrhage and wdio was unconscious from the time of the at- tack until his death, the ophthalmo- scope showed only moderate dilatation and tortuosity of the veins. These forms of amaurosis are not to be %9, AMAUROSIS (MAXSELL). confounded with the amblyopia of albuminuric retinitis, in which the vision is affected in several ways; by edema of the nerve-head, edema of the retina, hemorrhag"e in the foveal reg"ion. and patches of deg^eneration of that area. The diagnosis may be estab- lished by the ophthalmoscope. The writer describes 3 patients who were blind for longer or shorter periods after blows on the back of the head that did not fracture the skull. He ascribes the blindness to a traumatic affection of the occipital lobes, shock or hemorrhage, or both. L. Newmark (Jour, of Ophthal. and Otolaryn., May, 1914). Case in which the blindness came on gradually first in one eye and after some time in the other. There had l)een lancinating pains and some tendency to ataxia for a few months. The patient was a man of 49, and there was no history of headache or ocular paralysis. A number of cases on record teach tlie necessity for curing the syphilis in the secondary stage at least as the only means to certainly ward ofif atrophy. L. D. Espejo (Cronica Medica, Nov., 1917). Amaurosis in Hysteria. — Neuroses, the result of an unknown derange- ment of the nervous system originat- ing within the body or of traumatism, may reduce or altogether destroy temporarily the visual power in one or both eyes, rarely tlie latter. The traumatism may be ocular or involve any other part of the body. Tn order to induce blindness or even amblyopia the causative disease or injury must afifect an individual of peculiar or sus- ceptible organization and makes manifest a tendency toward magnifi- cation of trifles for the sake of bring- ing into prominence the ego or for the sake of imposition. In traumatic cases the diagnosis between hysteri- cal amaurosis and malingering is not always easy. Both offer no evidence externally or internally in the eye of any mark of injury or disease sufifi- cient to account for the symptoms. In hysteria the well-known stigmata may be found — tubular field, transient and recurring ocular paralyses, re- versal of the color field, well-defined patches of localized anesthesia of the skin, inexplicable and transient pains distributed anywhere and everywhere in the body and created by cleverly directed interrogation. Tlie majority of the subjects are women who are more or less mentally unbalanced by- disease of the sexual organs or by physical or mental idleness. The ma- lingerer is usuallv a man who resorts to the excuse of blindness in order to avoid unpleasant or dangerous duty or to collect damages from a rich cor- poration. The symptoms of hysterical amaurosis are altogether subjective and of cerebral origin. The eyes cannot be held responsible. Amaurosis in Spinal Disease. — Primary atrophy of the optic nerves preceding or accompanying disease of the spinal cord and spinal nerves is a common affection. It is "pri- mary" because it is initiated and carried to its finish without inflam- mation of the optic nerve visible to the ophthalmoscope. There is no edema or exudation. The disk mar- gins remain clear cut and well de- fined. The first noticeable change is a loss of the normal pink color on the temporal half of the papilla and a diminution of the size of both the arteries and veins of the retina. Gradually the vascularity becomes less, the nerA'e becomes paler and finally Avhite, all the fine vessels having become absorbed from the surface. Contemporaneously with the AMAUROSIS (HANSELL). 569 atrophic process the vision declines until complete amaurosis results. Early in the disease the field for colors is concentrically contracted or the perception of green is lost, and the retina becomes less sensitive to light or the optic nerve less capable of transmitting feeble stimulation. The affection is binocular, although one eye is usually more affected. Secondary atrophy, that following inflammation of the intraocular end of the optic nerve, presents entirely different ophthalmoscopic appear- ances, and no confusion need arise in the diagnosis between the two affec- tions. The diseases of which primary optic nerve atrophy is a prominent symptom are tabes, disseminated and lateral sclerosis, dementia paralytica, and paralysis agitans. The pupillary and visual disturbances may precede by many years the development of spinal affections, particularly posterior sclerosis, and many of the so-called idiopathic cases really belong to this class. The writer believes this is true also of paralysis agitans. He has at present a patient who seven years ago had incipient atrophy of the optic nerves with shallow excavation and for the past two years has slowly advancing paralysis agitans. Amaurosis following Hemorrhage. — After extensive loss of blood from any cause, but especially from disease of the stomach, intestines, or uterus, blindness affecting both eyes, com- mencing two or three days after the hemorrhage and advancing rap- idly, may ensue. The ophthalmoscope shows marked ischemia of the retina with low-grade edema of the nerve- head. The blindness may be complete and permanent, terminating in optic nerve atrophy ; or, in an individual with good recuperative power or when the loss of blood has been mode-rate, restoration of sight may be complete. Amaurosis in Pregnancy. — Toward the completion of the term of preg- nancy or during confinement, vision may be entirely suspended in both eyes for some hours or days. The amaurosis is usually associated with convulsions or other signs of puer- pural septicemia. It should be re- garded as a strong indication of intense and general poisoning. The fundus either shows no deviation from the normal or the retinal veins are distended and dark in color, the nerve-head is slightly edematous, and an occasional hemorrhage is found in the retina. After safe delivery, vision rapidly returns and the eyes are restored to their previous condition. Atrophy of the nerve and permanent amaurosis as a result of pregnancy alone have not, as far as the writer knows, been described, yet he has seen cases in which no other cause for the blindness could be assigned. Case of amaurosis gradually develop- ing in the course of pregnancy. The first signs of optic neuritis were noted about the fourth month ; both eyes were affected and external causes could be excluded. The optic nerve was atro- phied when the patient was first seen and the indications for interruption of the pregnancy were beyond question. Sight began to improve at once, and within two weeks vision was restored in the right eye. The other eye was first involved, and the nerve was atrophic beyond relief. The woman was a multipara of 37, with 8 children, and the author deemed it necessary to insure future sterility by an operation on the tubes. The case confirms anew the importance of immediate interrup- tion of the pregnancy in case of optic neuritis from this cause. Holzbach (Zentralbl. f. Gyniik., May 23, 1908). 570 AMAUROSIS (HANSELL). A form of amaurosis or amblyopia, not accompanied by ophthalmoscopic signs, or, at least, by none adequate to account for the condition, may supervene during pregnancy, parturi- tion, or the puerperium. Rarely it may assume the form of a hemianopic defect or of a central scotoma in the fields of vision, and still more rarely of hemeralopia (night blindness). It is often associated with such signs and symptoms of toxemia as head- ache, edema, eclampsia, and scanty urine containing albumin, casts, and blood. Recovery occurs, as a rule, within a few hours or days. Stephen- son (Ophthalmoscope, March, 1910). Amaurosis from Fracture of the Skull. — Numerous cases have been recorded of complete blindness of both eyes some months after a trau- matism of the skull. The common lesion is fracture at the apices of the orbits with or without involvement of other bones at the base. Hemorrhage from rupture of a large blood-vessel either anteriorly at the base or in- volvino- the basal or cortical centers of vision, a frequent complication of fracture of the skull, will destroy vision. In the latter lesion the amauro- sis is more rapid in its onset and temporary. Absorption of the blood is followed by gradual return of vis- ion unless the nerve structures have been destroyed by the insult or by pressure. Description of an epidemic of tran- sient blindness. Of 5 persons on board a small vessel soon after its arrival, 3 were taken suddenly sick and complained of loss of vision, but there was no fever; 2 died within 3 days, a man and a woman. The man who recovered became blind the fourth day. After 12 days of amaur- osis, vision gradually returned, al- though there were still evidences of optic neuritis. Three other cases of this apyretic amaurosis developed in the same locality, without contact with the first group. One of the men was just recovering from influenza. No causes of common intoxication could be discovered in the first group. Verger and Moulinier (Jour, de Med. de Bordeaux, Feb. 15, 1919). The writer urges that not a minute be lost before training those sud- denly blinded. Such a person is like a babe just born into a new world. From the very first, while still in the eye hospital, his training in writing with a guide frame and in reading the Braille type should begin, with- out waiting to ascertain whether vision is entirely lost or not. All the men could read and even write the Braille fluently by the time they left his service and had been initiated into manual labor, such as weaving rugs, making brooms and brushes, resoling shoes, or doing light garden work. Ginestous (Prog. Med., June 8, 1919). Congenital and Hereditary Amau- rosis.— Infants bcjrn with ocular or* cerebral defects, such as buphthalmus. micropbthalmus, or other deformities, or "amaurotic family idiocy," by which the essential parts of the eye or brain are wanting or so disturbed that function is absent, are hope- lesslv l)lind. Hereditary optic nerve atrophy, transmitted usually to males through the female line, appears sud- denly between the twentieth and thirty-fifth year as a loss of central vision. The scotoma increases and the periphery of the field becomes contracted until the patient is per- manently and totally amaurotic. Having found in the family history of an inmate of the Missouri School for the Blind the presence of cataract in all the members of the family for at least five generations, the writer after receiving the opinions of 152 oculists concludes as fol- lows: 1. All whose life work brings them into relationship with the blind should be aware of the dan- A M A I' R () SIS ( H A N S E L L ) . ?/ 1 gers connected with the marriage of a blind person. 2. The blind them- selves should be warned of the dan- ger to their children in case of mar- riage. 3. A distinction must be made between hereditary and non-heredi- tarj' forms of blindness. 4. Legal assistance should be invoked to pre- vent blind people from marrying. 5. This law should applj^ only to those cases of blindness in which heredity has been proved. With the exception of glaucoma and cataract, these dis- eases usually manifest themselves at or before the marrying age. 6. A law compelling every person to have an oculist's certificate before marriage, though idealistic, would be imprac- ticable. 7. The general public should be educated in the dangers arising from hereditarj^ blindness. C. Loeb (Annals of Ophthal., Jan., 1909). The causes of blindness in a series of 1100 children are classified by N. B. Har- man (Brit. Med. Jour., Aug. 29, 1914) into 3 groups: Injury or destruction of the cornea through surface inflammation with- in the eyeball or optic nerve; congenital defects of the eyes. Surface inflammation involved the eyes of 351 children, and of this number no less than 266 had ophthal- mia neonatorum, giving a proportion for this disease of 24 per cent, of the total cases of blindness. Only 47 cases were due to purulent conjunctivitis of later years, and 38 to phlyctenular keratitis. Syphilis was the cause of 190 cases of in- terstitial keratitis, of 126 cases of dis- seminated choroiditis or other blinding lesion of the posterior half of the eyeball, and of 16 cases of congenital blindness. Syphilis, therefore, accounted for a total of 343 cases of blindness, or 31.7 per cent, of the whole 1100 cases, or of considerably more than were due to gonorrheal infec- tion. This is in part the result of the recent more or less general use of some prophylactic agent in the eyes of the new- born to prevent gonococcic infection. Since 1904 the figures show that there has been a definite reduction in the pro- portion of cases of blindness due to the gonococcus, while the proportion due to syphilis has risen. In a study of the causes of l^lindness, H. L. Gowens (Hahn. Mthly, Apr., 1914) shows that 88.58 per cent, of all blindness is prevental)le as against 11.42 per cent, in- curable and non-preventable blindness. Even after eliminating purulent ophthal- mia and high myopia there still remains 85 per cent, as a percentage of blindness which is conceded to be preventable blindness as against 15 as a percentage which is non-preventable and incurable. H. H. Stark (Jour. Amer. Med. Assoc, Oct. 30, 1915), in reporting cases of eye complications of sinus disease, reviews the literature. Of 88 cases reported, the optic nerve was involved in 52. Variations in the pupil occurred as one of the earliest symptoms. Exophthalmos occurred in 11, and involvement of the extrinsic muscles in 11. Central scotoma was the most defi- nite, and the one on which the author most relies. W. H. Bates (X. Y. Med. Jour., Feb. 3, 1917) cites a case in which he employed a new method of treatment for a develop- ing glaucoina, and a previous gradual loss of sight for 25 years. The patient, a woman, had received treatment from many phj-sicians for her eye conditions during this time. Bates treated her for the following conditions: Incipient catar- act, vitreous, cloudy with floating bodies; neuritis, with partial atroph}^ of the optic nerves; retinitis, with obliteration of many blood-vessels; choroiditis dissem- inata; glaucoma of the left eye; connective tissue in the anterior chamber of the left eye, obscuring the iris and pupil; func- tional mj'opia; functional divergent and vertical squint. An acute glaucoma de- veloped and was treated at first by drugs. With the assistance of Dr. C. Barnert an iridectomy was performed, and while pain and tension were relieved, the vision was not improved. Mild, recurrent attacks of glaucoma occurred. Bates then employed the central fixation method of treatment, and obtained such excellent results that the patient at the end of a comparatively short time was able to travel on the sub- way, attend social functions, and could see clearly the lights across the Hudson River. In 6 days the sight of the right eye had improved to more than V^o of the normal. The method demands the use of -:'72 AxMBLYoriA (1 1 AXSELL). the memory and the imagination. A small black spot on the Snellen card was imagined, and at the beginning of the treatment, the period imagined was im- perfect. The patient had to imagine this spot as perfectly black and stationary at all times; then to be conscious of seeing a part or all of a letter without losing the period. Central fixation meant to her a passive or relaxed condition of the eyes and brain. The ol)jective symptoms all disappeared instantaneously when the pa- tient was conscious of central fixation, and the organic lesions were gradually seen to improve. With the blood-vessels the changes were more slow; but with the cloudiness of the lens, central fixation was followed immediately by an increased transparency. Howard F. H.vnsell, I'hiladelphia. AMBLYOPIA. — DEFINITION. — The word "amblyopia" signihes. without specializing the cause, that Ithe acuity of vision is below the nor- mal. The degree of the loss of vision is not suggested by the word itself, nor has there been any attempt, as far as I am aware, to define its lim- itations. It has been inherited from the preophthalmoscopic times, when the two words amblyopia and amau- rosis were commonly used, the former to mean dull vision and the latter, blindness. [Today we seldom hear of amaurosis, but we have tenaciously held to ambly- opia. Its use is convenient, but unless preceded by a descriptive adjective, such as toxic, hysterical, its meaning is indefi- nite and vague. The sense in which the word is properly used is the express par- tial loss of vision due neither to dioptric abnormalities nor to visible organic lesions, or, as expressed by the older writers, "amblyopia without ophthalmos- copic appearances." It is, therefore, not a disease, but a symptom, and is due to many different and varied causes. H. F. Hansell.] The varieties of amblyopia are usually classified into organic from toxic and intracranial causes, func- tional exanopsia (disuse, non-use, argamblyopia) ; hysterical, simulated, and from exhaustion. Toxic Amblyopia. — The ingestion of or absorption into the system through the lungs, intestinal tract, or skin, of large quantities of certain substances without adequate elimination, or of small quantities in the case of some susceptible organisms, will produce a loss of vision varying in degree from slight up to total blindness. The com- monest agents are alcohol and tobacco in combination, lead, quinine, methyl alcohol, Jamaica ginger, coffee, mer- cury, phosphorus, chloral, opium, er- got, the salicylates, ptomaines. The sight is affected by these substances in several ways — by altering the con- stituency of the blood and lessening its nutritive value to the ocular struc- tures ; by exciting disease of the re- tinal nerve-cells leading to degenera- tion of the cells and of the optic-nerve fibers connecting them with the brain- centers and inducing structural changes in the centers for vision. The amblyopia may be acute, as in quinine and methyl alcohol, or chronic, as in tobacco and alcohol poisoning. The symptoms common to the chronic form are : — Loss of Vision. — The deterioration is gradual and is usually neglected by the patient until the ability to read is diminished or abolished. Examina- tion shows that vision has fallen to one-half or more for distance and near and is not to be improved by glasses. The patient complains of a bluish-gray smoke or mist constantlv before the eyes, and of partial night-blindness. He has no pain and rarely phosphenes or AMBLYOPIA (HANSELL). S7Z other signs of irritation of the retina or nerve. Central scotoma, either relative (col- ors only ) or absolute. Early in the affection, probably contemporaneous with the beginning of the deterioration of vision, the perception for green in the small region of the field controlled by the fovea centralis is lost. Then follows the perception for red and possibly blue. The scotoma may be confined to these colors. Should the disease advance, the scotoma becomes absolute, the perception of all objects being lost in an area of about 10° from the fixation point. The periph- ery of the field retains its normal dimensions until the onset of optic nerve atrophy, when it undergoes a concentric narrowing. Papilla Changes. — The ophthalmo- scope shows in nearly all instances a whitening of the temporal half of the papilla, with retention of the normal coloring and vascularity of the nasal half. The retina and choroid are un- changed. Even the macula, the point of the fundus which is symptomatically most involved, appears healthy. In about one-third of the cases the optic disk is slightly hyperemic early in the disease and the vessels on the disk are veiled, reflecting the earliest signs of optic neuritis. Acute poisoning from absorption of methyl alcohol, quinine, pure spirits, etc., causes sudden and complete blind- ness, even to the loss of perception of light. The action of the poison may be sudden or cumulative. A man of 35 was exposed by the nature of his occu- pation to the fumes of varnish. He absorbed them through the lungs and the skin of the hands and arms. Feel- ing in his usual good health when he went to bed, he was awakened several hours later by some cause unconnected with his eyes and discovered he was totally blind. Examination of his eyes the following day disclosed excessive anemia of the disks. The arteries and veins of the retina were invisible a short distance from the nerve-head. A boy of 19 drank an unknown quantity of "white whisky" (95 per cent, alco- hol). He was blind the next morning and, except for the temporary return of perception of light lasting a few days, remained blind. The ophthalmo- scopic appearances were similar to those in the former case. The promi- nent symptoms of acute toxic amblyopia are illustrated by both cases : Sudden and complete blindness, partial tempo- rary recovery, ischemia followed by atrophy of the optic nerves and retinas, and permanent blindness. Amblyopia from Intracranial Causes. — In the preceding paragraph the morbid processes are presumed to be limited to the nervous mechanism of the eye, lying anterior to the chiasm or, if they invade the cerebral tissues, the involvement is secondary and may be considered as a complication. In the intracranial amblyopias the original le- sion is cerebral, the secondary in the optic nerves and retina. Uremia of Bright's disease, of pregnancy, and of scarlet fever is a common cause. The amblyopia is usually binocular, rapid in its course, and leads often to complete, but temporary blindness. The prognosis is good. No changes in the eye-grounds commensurate with the degree of loss of vision are to be seen. The retinal veins are dis- tended, dark, and tortuous, and the edges of the disk veiled by edema of the nerve and adjacent retina. The cerebral vessels present a similar condition, namely, reduced supply of 374 AMBLYOPIA (HAXSELL). arterial l^Iood, venous stagnation, and diffused serous exudation into the brain substance. The foreign elements con- tained in the blood doubtless are a con- tributing cause to the disturbed brain functions. With the establishment of free secretion of urine or artificially induced active diaphoresis the poison is eliminated from the blood, the serum absorbed, and the vision and cerebration restored ; or, the kidneys refuse to act, the skin cannot be stimulated, and death ensues. Rarer forms of amblyopia due to obscure intracranial lesions are the "crossed" and the "hemianopsias." Mills says (Posey and Spiller) : "As the fibers of the macular bundles are undoubtedl}' distributed to the pre- geniculatum, complete destruction of this body, or of a special portion of it, would cause central amblyopia of the crossed variety." In the hemian- opic variety one-half of the macular field is lost and the other half pre- served. Thus one-half of a word or other small object close to the eyes is obscured and can be seen only by movement of the ball. In explana- tion Mills further says: "A strictly limited lesion of the calcarine cortex on the one hand and of the angular region on the other may cause blindness in half of the macular field of the cor- responding sides." Hysterical Amblyopia. — The fea- tures characteristic of this affection are partial or complete blindness, monocu- lar or binocular, without discoverable changes in the ocular structures or signs in the eye or elsewhere in the body of organic disease of the brain or nervous system. The loss of vision may arise spontaneously, or appear at the termination of an attack of general hysteria, or be due to a slight trauma- tism to the eye or head. The trau- matism is, as a rule, slight and out of all proportion to the seriousness of the subsequent complaints. Amblyopia may be the only ocular symptom or it may be complicated by ptosis, recession of the near-point, pupillary inequalities, or disturbances in the field of vision. The alteration in the size and form of the field presents three possible fea- tures : concentric contraction, which is not in the least characteristic of hys- teria ; reversal of the normal limits of the color fields, and the tubular field. Traumatic cases recover promptly and wholly after the cause, for instance a suit for damages, is removed. Cases of spontaneous origin and those dependent upon functional derangements of the nervous system are more persistent, often recur, continue weeks and months, and recover only upon the restoration to health of the individual. It must not be forgotten that blindness without ophthalmoscopic findings or evidence of disease of the cerebrospinal system may not always be diagnosed as hys- terical, and that it may have an organic cause to become manifest in time. To make the diagnosis positive it should be associated with at least some of the well-known stigmata of hysteria. Simulated Amblyopia. — The differ- ential diagnosis between simulated and hysterical amblyopia is rendered diffi- cult by the similarity of the two affec- tions and because both occur in the same class of patients, the neurotic and those of hypersensitive organizations. Pretended, feigned, or simulated blind- ness is found among recruits for the army and navy services, those who wish to escape positions in which danger or punishment may be incurred, and those who wish to create false impressions and exaggerated estimates of their AMBLYOPIA (HANSELL). 0/0 physical disabilities, especially in law- suits for damages. Simulated am- blyopia of both eyes is rare and detec- tion difficult. Reliance must be placed on the action of the pupils and the want of relation between the apparently nor- mal eyes and the symptoms. The mo- nocular form, however, may be, as a rule, easily detected. The ophthalmo- scope shows clear media and healthy eye-grounds ; a strong spherical lens placed before the sound eye will prevent accurate vision in that eye beyond the focal distance of the glass ; a prism of 5°, base down or up, will give vertical diplopia; a prism of 10°, base out, will cause a manifest rotation of the eye inward, unconsciously made to fuse the horizontally induced double images ; a lead pencil placed before the sound eye will not interrupt reading; the pupils respond to light and convergence almost uniformly. The tests will more suc- cessfully deceive the patient into admit- ting visual power in the assumed bhnd eye if his attention is directed by them to the sound eye. Radiography is also valuable in the diagnosis. An individ- ual may claim that the blind eye con- tains a fragment of glass or other foreign material impervious to the rays. In such cases a shadow is cast on the plate when the claim is true. In trolley accidents it frequently happens that the glass of the doors or windows is shattered and the hysterical or fraud- ulently inclined passenger asserts that he was blinded by the entry and reten- tion in his eye of glass. Examination with the ophthalmoscope cannot inva- riably exclude the presence of the foreign body, particularly when it has lodged in the ciliary region or when the media are clouded. Amblyopia Exanopsia. — From con- genital defects in the ocular structures, such as cataract, polar and lamellar; coloboma of the lens or uveal tract ; persistent pupillary membrane ; albi- nism. Rays of light are obstructed in their passage through the eye by the opaque media, they are not clearly focused on the retina by reason of irregular refraction, or they fall upon insensitive retinas or those unsupported by choroidal pigment. In these cases it is probable that early in life the retinal centers in the brain are active and do not, either by disease or congenital anomaly, contribute to the blindness. The cataracts may be removed and vision restored when the operations are performed at an early age. Later, when the brain-centers have been trained and the habits of special sense perception have been formed, operations, although surgically successful, do not materi- ally improve vision. From Defects of Refraction. — In grades of hyperopia from 2 D. to 5 D. in childhood, binocular vision may early become unattainable. The child uncon- sciously, in order to obtain good vision, makes extraordinary claims on the ac- commodation. But the ciliary muscle (accommodation) is supplied by nerve power by the third or motor oculi nerve, wdiich also supplies the muscles of convergence. Therefore, excessive stimulation of accommodation or that surpassing the normal relation between accommodation and convergence com- pels a proportionately equal degree of convergence. Since both eyes can- not converge simultaneously in dis- tant vision, one eye assumes the abnormal convergence and the other eye is used for fixation. Both eyes retain their normal power of rotation, but each becomes in a sense inde- pendent of the other: the one is used for seeing; the other squints. The ?7(^ AMENORRHEA (MONTGOMERY). former has been the better eye from tlie beginnini*", either l)v reason of less error of refraction or more per- ceptive retina. The latter gradually becomes amblyopic from disuse. The retina loses its sensibility, the optic nerve its conductility, and the cerebral centers their function. In some chil- dren no reason can be assigned for preference of one eye. The error of refraction may be no greater and the rotatory power no less in the squinting than in the fixing eye. Here we must assume that the fault lies in the retina, nerve, or brain. Improvement of vision may be obtained by the forced use of the eye and tlie compulsory activity of the cerebral center, but vision equal to that of the non-squinting eye is seldom or never acquired unless the usefulness of that eye is destroyed by accident or disease. Habit and the cultivation of the visual apparatus that accrues from habit can not be ignored. Should, however, the treatment for defective vision be instituted very early, before anesthesia of the nervous apparatus of the squinting eye has developed, an appreciable benefit may be gained by the use of the amblyoscope, closure of the fixing eye by bandage, or atro- pinization of that eye. Amblyopia from Exhaustion. — Am- blyopia in consequence of excessive indulgence in coitus or masturbation has been recorded. It is a purely nervous afifection. Upon removal of the cause and the administration of strychnine the cure is generally rapid and complete. Sudden loss of blood in large quantities, occurring sometimes in intestinal ulceration, after delivery of the child in confinement, rupture of blood-vessels by ulceration or accident, may be followed in a few hours by temporary loss of vision. The ambly- opia Ijecomes permanent only in cases of degeneration of tiie ganglion cells of the retina or of the fillers of the optic nerve. Howard F. Hansell, Philadelphia. AMENORRHEA. — D E F I N I - TION. — Absence of the menstrual flow in women of a suitable age who are not pregnant. Suppression of menses, the menstruation having ceased through some local or remote disorder, is also termed amenorrhea. VARIETIES. — Amenorrhea mav be complete, v/hen the menstruations will have completely ceased; comparatk'C, when it appears occasionally; primary, when the menstruation has not pre- sented itself at the age of puberty nor subsequently ; secondary, when transi- tory or accidental, or, having already appeared, the menstruation ceases. SYMPTOMS.— Xo other symptom than absence of the menstruation may be present, or the monthly flow^ may be absent and the general attendant phenomena usually preceding men- struation occur. I'requently the pa- tient complains of headache, heat- Hashes, fever, nausea and vomiting, and lieaviness in the abdomen. Con- comitant nervous disorders may form the basis of acute manifestations, hysterical especially. When the amenorrhea is due to obstruction, Vihether congenital or acquired, tlie patient does not experience severe pain, but rather a continuous dull aching in the pelvis and over the sacrum, aggravated at the periods when the menstruation should occur by the symptoms above mentioned, known as menstrual molimina. Pure suppression of the menstrua- tion rarely causes symptoms, espe- AMENORRHEA (MONTGOMERY). 177 cially when the impending- general disorder is the cause of the amenor- rhea. The menstrual flow may be sub- stituted by a profuse leucorrhea which is thick, viscid, and of a yellow or greenish-yellow color. Remote symp- toms may present themselves, doubt- less of reflex origin. ETIOLOGY.— The discussion of the causes of amenorrhea is rendered difficult by our want of knowledge of the forces which produce the periodi- cal recurrence of menstruation. Pri- mary amenorrhea is generally due to imperfect or insufficient develop- ment. In cold countries the individ- ual matures more gradually and the menstrual flow appears later than in warm countries, where development is rapid, but where, also, women enter stages of decrepitude at an earlier date. Anatomical imperfections and anomalies, the absence of any of the genital organs, or a rudimentary or infantile uterus may thus account for the total absence of menstruation. Imperforate hymen is a frequent, though easily recognized, cause of amenorrhea. Whether we ascribe the periodi- cal occurrence of menstruation to nervous irritation, to the influence on the mucous membrane of tlie uterus of a superabundance of lime salts in the blood or to the chemical influence through the blood of a secretion of the corpus luteum, the causes of amenorrhea can be divided into four classes : — Many cases of amenorrhea are traceable directly to absence of cor- pus luteum owing- to the degenera- tion of unruptured follicles. This probably accounts for the good re- sults obtained in some cases from corpus luteum organotherapy. Emil Novak (N. Y. Med. Jour., June 17, 1916). An increase in amenorrhea has been observed since the beginning of the war, in young girls who have reached puberty. Amenorrhea is not infrequent in cases where the condi- tions of life are changed at the time of puberty. In the present instance the change is one of diet. This dif- fers from the pre-war diet in poverty of flesh and fat. There is also a pro- longed physical and intellectual weak- ening. M. Graefe (Miinch. med. Woch., Ixiv, No. 18, 1917). Nervous Disorders. — Grief, anxiety, fright, and anger are as many possible primary causes, especially if the patients are poorly fed. According to Bloom, probably not less than Z'i per cent, of women emigrants under 30 years of age sufi'er from suppressed menstruation after a sea-voyage. Many have abdominal distention, and not infrequently girls have been in- nocently charged with being preg- nant. Obstinate constipation is a common symptom. The true etiology is largely psychical and neurotic. The causes of primary amenorrhea at puberty not due to congenital atresia may be distinguished into three varieties, viz.: 1. Cases with- out discoverable cause, in which the genital organs are apparently per- fectly normal. 2. Those due to some congenital defect. 3. Amenorrhea ac- companying some general disease, as diabetes or tuberculosis. In the first, local or general treatment may cause appearance of the menses, the prqg- nosis in the other two varieties being unfavorable. The writer cites a case in which inenstruation occurred after grafting of a healthy ovary from an- other subject in the uterine wall. V. le Larier (Paris Thesis; Zentralbl. f. Gynak., Nu. 35, 1905). Women who either greatly fear or greatly desire to become pregnant, newly married women, and women -37 578 AMENORRHEA (MONTGOMERYV who are confined in prisons or insane- asylums furnish a large proportion of the cases. Removal from country to city or vice versa, especially when coupled with nostalgia, is a prolific cause. On general principles, change in the mode of living or of climate, especially with an intervening sea- voyage, appears to frequently act as the etiological factor. Amenorrhea may be an early symp- tom of brain tumor and in acromegaly may precede every other symptom by several months and be followed by optic atrophy. General Affections. — Amenorrhea frequently occurs after a serious ill- ness, such as typhoid fever, eruptive fevers, mumps, pneumonia, or during the course of any chronic disease, diabetes, cancer, malaria, at the onset of severe syphilis. Intoxication of the S3^stem, as in morphinism, alco- holism, and hydrargyrism, is also a recognized cause. ^Syphilis is also thought capable of causing amenor- rhea. Lutaud, of Paris, reported 18 cases in which tiie morphine habit caused amenorrhea. It is usually complete and accompanied by loss of sexual de- sire, but the functions are re-estab- lished if the habit be broken. Three cases, aged from 28 to 42, in which amenorrhea persisting from six to eight years was probably due to syphilis. They all exhibited char- acteristic symptoms of tertiary syph- ilis, and were subjected to a rigid mercury and iodide treatment which resulted in the return of the men- strual flow. Meirowsky and Franken- stein (Deut. med. Woch., Aug. 4, 1910). The writer observed a case in which the amenorrhea was due to an X-ray examination. The patient, a girl of 14, robust and of a good fam- ily, had swallowed a needle, and was examined for 3^ hour with the X-rays, which entailed a severe der- matitis. Although she had been men- struating for nearly 2 years, she ceased to do so after the X-ray ex- posure. After 3 months she began to have severe headaches and at times abdominal pain, especially in the left flank. Ovarian treatment, mustard foot baths and purgatives, applied at the approximate menstrual dates failed to bring any result. Siquot (Rev. Med. del Rosario, Aug., 1918). It may be consequent upon an acute or chronic surgical affection, a blow, or injury. Luxurious living and want of exercise, obesity, and excessive in- tellectual labor at the period of puberty, when not counterbalanced by fresh air and active exercise, may retard the development of the genera- tive organs and thus induce the disorder. Blood Disorders and Wasting Dis- eases.— .\nemia and idiopathic chlo- rosis, pernicious anemia, leukemia, and Hodgkin's disease are the most prominent factors. The following causes of waste — and directly, there- fore, of amenorrhea — are also to be remembered : Hemorrhage, albumi- nous discharges ; hemorrhage from piles, scuny, purpura, and injury, as in hemophilia; hemorrhage from the stomach, as in gastric ulcer ; from the lungs, or from the nose, and from a rare disease produced by a parasite in the duodenum: the Ankylostoma duodenale. Long-continued suppura- tion, albuminuria, chronic diarrhea, malignant ulcers, tubercular disease, all impoverish the blood, and so may cause anemia. All diseases that cause wasting of the body finally cause the menstruation to cease. Chief among these are phthisis, dia- betes, caries of bone, protracted or AMENORRHEA (MONTGOMERY). 579 febrile illness; anorexia nervosa, the patient wasting because she will not eat ; and gastric ulcer. The occurrence of menstruation is associated with increased vascular ten- sion ; hence, any condition which de- creases tension will favor amenorrhea. Lesion of Genitourinary Organs. — Amenorrhea may be associated with any lesion of the genital tract, though less likelv to occur in intiammatory conditions. Adhesions from pelvic peritonitis are an occasional cause of hyperinvolutions of the uterus and amenorrhea as a symptom. Atrophy of the ovaries, senile atro- phy following pregnancy, and cystic ovarian degeneration are among the less common etiological factors. A most complete examination of the pelvic organs, under ether, if neces- sary, should be made in such cases. Exposure to cold during menstrua- tion, by inducing congestion of the pelvic organs, is one of the most active exciting causes, especially when supplemented by a local chronic disorder. The most important condi- tion with which this disorder might be confounded is pregnancy. PATHOLOGY.— A pathological identity can hardly be attributed to amenorrhea, owing to its complex causes, the diverse physiological con- ditions peculiar to the cases, and the diathetic conditions that may be present. The fact that the true nature of menstruation itself is un- known adds another objection, and it may safely be said that the pa- thology of amenorrhea is that of the diseases causing it, until the local disorders brought about by each will have been determined. DIAGNOSIS. — Primary amenor- rhea— that is, total absence of men- struation— is usually due, as already stated, to the absence of one or more of the organs of generation. It must be distinguished from retention of the menses due to atresia of the cervical canal, of the vagina, or of the vulva. In the latter case no menstruation has existed, but the general premonitory symptoms of menstruation have oc- curred, though followed by no men- strual flow. Cases in which one or more of the organs are absent are not very infrequent, while cases of im- perforate hymen are comparatively common. PROGNOSIS,— Amenorrhea due to absence of any of the organs is, of course, incurable. The same may be said where the approach of the meno- pause or other conditions point to pre- mature senility of the uterus, which involves the inhibition of the men- strual period. Although amenorrhea, when due to a serious chronic disease, is usually cured with difficulty, hope may always be entertained when the causative disorder is not in itself a fatal one. Return of the menstrua- tion in any chronic disorder, when the blood presents its normal appearance, is an encouraging sign. TREATMENT. — No woman should be treated for amenorrhea until the possibility of its being caused by pregnancy has been elimi- nated, if necessary by a careful physi- cal examination. Not infrequently will pregnant women desirous of escaping the responsibilities of mater- nity seek a consultation with the hope that some drug shall be administered or instrument inserted which will. ter- minate the condition. Amenorrhea should always arouse concern; it may be the first symptom of acromegaly, to which it stands in 580 AMENORRHEA (MONTGOMERY). about the same relation as ordinary goiter does to exophthalmic goiter, the hypophysis cerebri being so often in- volved. The amenorrheic should take special pains to avoid chilling, especially of the feet, and every catarrhal affection should be treated with great care. Three such patients in the writer's practice had previous sinusitis, commencing in 1 case at the time the menses became irregular. Special care should also be paid to treatment of syphilis in this connec- tion. Rosenbergcr (Zcntralbl. f. in- nere Med., Feb. 25, 1911). Curetting was found to aid in the restoration of menstruation in a large number of 111 cases of amenorrhea. The uterine mucosa undergoes cyclic changes even without the menstrual hemorrhage. The scraps obtained by curetting show whether the mucosa is comparatively normal or atrophied. By this means the writers discovered in 5 cases in the uterine mucous mem- brane a tuberculous process which had never caused symptoms. Novak and Graff (Zeit. f. Geburtsh. u. Gyniik., Apr. 5, 1921). It should be kept in mind that amenorrhea is a symptom, and its cause be diUgently sought as a prelimi- nary measure to treatment. Drugs which are considered to exert an in- fluence in promoting the menstrual flow are known as emmenagogues, and are divided into two classes, medicinal and physiological. Severe physical shock or fright sometimes causes the menstruation to return suddenly. When the arrest of menstruation is due to exposure to cold, warm baths and vaginal injections, sinapisms to the thighs and calves of the legs, saline laxative and manganese-bin- oxide pills (2 grains each), 1 or 2 after each meal, are frequently suc- cessful. This drug- acts by increasing the vascularity of the pelvic organs. The permanganate of potassium, or the lactate, in 1 -grain doses three or four times daily, after meals, act in the same manner. Potassium permanganate may be given daily until the catamenia ap- pear and complete their course, when the salt should be discontinued; it should be recommended four days before the access of the next period, and continued until the flow ceases. It is useful in girls who, on leaving the country and coming to town, suf- fer from arrested menstruation; also in the amenorrhea induced by sea- sickness and in the case of women, between 30 and 40, generally mar- ried, who while rapidly increasing in weight suffer from a diminished men- struation. Potassium permanganate is given up to 1, 2, or more grains in I)ill form thrice daily, after meals. The pills should be made after the following formula: Potassium per- manganate, gr. j ; kaolin and petrol- eum cerate, in equal parts, q. s. Cer- tain observers deny that the per- manganate produces abortion, but some cases of abortion apparently due to the drug have been observed. (Practitioner, Feb., 1911). In the amenorrhea following sea- voyages the preparations of manganese and oxalic acid hold the first place. When the manganese preparations fail, santonin, 10-grain doses at bed- time, is especially valuable in chlo- rotic subjects. The general system should be in- vig-orated by attention to diet, sleep, and clothing. Out-of-door life, light exercise, and sunlight are most im- portant. This is especially the case when there is rapidly increasing obesity. In the latter case the diet should be regulated, saline laxatives adminis- tered, or a cure at Marienbad recom- mended. The administration of thy- roid extract is especially effective in premature menopause from obesity, AMMONIA (SAJOUS). 581 and should be associated with active exercise. Stimulation of the ovaries and uterus by the faradic current is especially efficient in such cases. Cupping or scarifying the cervix is sometimes successful. These means increase the pelvic congestion and tend to counteract uterine or ovarian torpidity. Rudimentary organs or atrophy of the uterus, if not too great, should be treated by dilatation of the uterus w^ith tents and stimulated by the faradic current. The introduction of a stem pessary ^vhich is to be worn for a number of months not infre- quently increases the growth of a rudimentary organ and establishes the function of menstruation. Exer- cise and nourishing food should also be given. Sea-bathing is of assistance in such cases. In amenorrhea due to infantile uterus the writer recommends hy- gienic and tonic measures; the uterus slowly dilated with graduated dila- tors; iodine or 95 per cent, phenol ap- plied to the endometrium; and later the insertion of a stem pessary and the careful administration of thyroid extract or corpus luteum, given con- tinuously OA'er a considerable period of time. Loop (N. Y. State Med. Jour., Apr., 1917). The rheumatic diathesis occasion- ally plays a part as an etiological factor. In such cases the ammoniated tincture of guaiac, 1 dram in milk three times a day, or the tincture of colchicum root, 10 drops every three hours until the bowels become free, will sometimes restore arrested men- struation. The salicylate of sodium is also valuable in this connection. Apiol, 4 grains daily in 1-grain pills, for fifteen days, has given good results. Fuchsin has been highly rec- ommended as an effective drug in re- establishing the menstrual flow. Electricity is of great value, fara- dism, static electricity, galvanism, and galvanic intra-uterine pessaries being applicable according to the nature of the case. Extract of cows' ovaries fresh cor- pus luteum has been used with success, (see Animal Extracts: Ovarian Or- ganotherapy). The writer reports 20 cases treated by hypodermic injections of pituitrin or hypophysin. Pie has seen no bad effects, and a sufficient number of cases have been cured or improved to make the treatment worth trying. Rushmore (Boston Med. and Surg. Jour., Mar. 2, 1916). E. E. Montgomery, Philadelphia. AMIDOACETPHENETIDIN HYDROCHLORIDE. See Pheno- coLL Hydrochloride. AMINOFORM. See Hexamethy- lenamine. AMMONIA. — Ammonia, chemi- cally NH3, is made in large quantities from coal gas by heating the ammo- niacal liquor with calcium hydroxide, thus conducting the gas formed through tubes containing charcoal. It may be conveniently obtained in smaller amount by heating an ammonium salt, such as ammonium chloride, with dry caustic soda (sodium hydroxide) or slaked lime (calcium hydroxide). It can be formed by the direct union of nitrogen and hy- drogen under the electric spark, and is widely produced in nature through the putrefaction of albuminous substances. PROPERTIES.— Ammonia is a transparent, colorless gas, having an extremely pungent odor and acrid taste. It is strongly alkaline in reaction, and 582 AMMONIA (SAJOUS). dissolves very readily (to the extent of Ointment of ammonia, composed of 700 volumes) in water, forming a strong ammonia water, 17 parts ; lard, 32 parts ; solution designated as ammonium hy- oil of sweet almonds, 2 parts, droxide (sp. gr., 0.897 at 25° C, U. S. MODES OF ADMINISTRA- P.). TION. — Ammonia is miscible in all PREPARATIONS AND DOSE.— proportions with water and alcohol. The preparations of ammonia included The most agreeable preparation for in- in the U. S. Pharmacopoeia are as fol- ternal use is the aromatic spirit, which lows : — should always be given well diluted with Aqua ammonicc (ammonia water, water. As a stimulating inhalation, the hartshorn), containing 10 per cent, by gas arising from ammonium carbonate weight of ammonia gas; dose, 10 to 30 (the ordinary "smelling salts") is f re- minims (0.6 to 2.0 c.c). quently employed; but this may readily Aqua ammonicc fortior (stronger am- be replaced by the simple ammonia wa- monia water), containing 28 per cent, ter, or. if adflitional care is used, by the by weiglit of ammonia gas; used chiefly stronger ammonia water. The spirit externally as a vesicant. and the water of ammonia have also Spiritus ammonicc (spirit of ammo- been administered hypodermically, or nia), an alcoholic solution, containing even intravenously, as stimulants, though 10 per cent, of ammonia; dose, 10 to 30 their action is but fleeting, and consid- minims (0.6 to 2.0 c.c). erable local irritation, may arise. In Spiritus annnonicc aromaticus (aro- pneumonia and other dyspneic states a matic spirit of ammonia), composed of little ammonia water dropped into boil- ammonium carbonate, 34 parts by ing water at frequent intervals will weight ; ammonia water. 90 parts by "soften" the atmosphere and greatly volume; oil of lemon, 10 parts; oils of facilitate breathing, lavender flowers and of nutmeg, of each. Externally, the stronger ammonia 1 part ; alcohol, 700 parts; water, enough water may be applied in full strength to make 1000 parts. A nearly colorless as a vesicant, and the area under liquid when fresh, but gradually becom- treatment should be covered with a ing darker; dose, 30 to 60 minims (2.0 watch-glass to prevent evaporation, to 4.0 c.c). For counterirritant efifects,a 10 percent. Lininicntuni ammonicc (ammonia lini- aqueous preparation, such as the weaker ment), composed of ammonia water, ammonia water, or a stronger oily prep- 350 parts by volume ; alcohol, 50 parts ; aration, such as the official ammonia cottonseed oil. 570 parts; oleic acid. 30 liniment, is suitable. In children with parts. Should be freshly prepared when delicate skins these preparations should wanted. be further diluted. In spasmodic croup The following non-official prepara- a little ammonia added to water and ap- tions have also occasionally been used : — plied to the child's neck and chest by Fetid spirit of ammonia, composed means of a cloth will often bring con- of asafetida, 1 part ; spirit of ammonia, siderable relief, though much care is re- 21 parts; dose, 30 minims (2.0 c.c). quired to have the fluid sufficiently di- Camphorated ammonia liniment, com- lute and not to leave it on too long. The posed of ammonia water, 30 parts ; cam- evanescence of the effects of ammonia phor liniment, 70 parts. resulting from its volatility requires AMMONIA (SAJOUS), 583 that its administration be frequently re- peated. INCOMPATIBLES.— Mineral or vegetable acids and acid salts, which ammonia neutralizes with the formation of neutral salts; salts of the alkaloids, which ammonia may cause to be precip- itated by combining with the acid radi- cal (thereby setting free the more or less insoluble pure alkaloid) ; chlorine, bromine, and iodine, with which ammo- nia combines to form corresponding salts ; mercurial and most other metallic salts, with which ammonia forms in- soluble mixed salts or hydroxides. CONTRAINDICATIONS.— In acute inflammations of the stomach and in cases where the urine is abnormally acid the internal use of ammonia is to be avoided. In small children and in persons with a sensitive respiratory tract, the inhalation of ammonia fumes is likewise apt to be prejudicial, large amounts giving rise to a bronchitis. PHYSIOLOGICAL ACTION.— Local Effects. — Solutions of ammonia strongly irritate any tissues with which they may be brought in contact. Ap- plied to the skin, they act as rubefa- cients or vesicants, according to the con- centration of the preparation used and the length of time it is left on the tis- sues. On the mucous membranes, es- pecially the conjunctivas, the buccal and the respiratory mucosae, ammonia vapor acts primarily as a stimulant, exciting the local nerve-terminals, causing in- creased flow of glandular secretions, and, when concentrated, spasm of the glottis ; when kept in contact for a longer time, ammonia preparations cause inflammatory changes which may result in local death of the tissues, fol- lowed by sloughing. The caustic action of ammonia is due, as is the case with other alkalies, to a combination with the tissue albumins, resulting in the forma- tion of alkali albuminates, and with the fats to form soaps. The great penetrat- ing power of ammonia, due to its vola- tility, renders it, when concentrated, one of the most deeply acting of corros- ives. Effects on Internal Use. — Nervous System. — ^After being absorbed into the circulation, ammonia stimulates, for a short period, the medulla oblongata and the motor side of the spinal cord. The higher brain-centers are, if anything, slightly depressed. The spinal stimula- tion results in an exaggeration of re- flex activity and, with excessive doses, in convulsions. Succeeding the stage of stimulation, a secondary stage of de- pression of the medullary centers and spinal cord may occur with large doses. Circulation. — Ammonia stimulates the heart muscle, the vasomotor center in the medulla, and, to a less extent, the inhibitory (vagus) center, likewise in the medulla. These effects result mainly in a pronounced rise of the general blood-pressure. The heart beats more strongly, but its rate is frequently slowed. Excessive doses may lead to a secondary depression of both the heart and vasomotor mechanism. Respiration. — The respirator}^ centers in the medulla are strongly stimulated by ammonia. Both rate and depth of breathing are increased through its ac- tion. Secretions. — Ammonia and the am- monium compounds stimulate the flow of body secretions, especially the sweat, saliva, and mucous secretions. The dia- phoretic eflfect is believed to be wholly central, i.e., due exclusively to excita- tion of the sweat-center in the medulla. The other secretory eft'ects are ascribed both to a central action and to a local ettect on the gland-cells. 584 AMMONIA (SAJOUS). Digestive Tract. — Moderate doses of TOXICOLOGY. — The ingestion of ammonia stimulate, like other alkalies, strong solutions of ammonia results in the gastric glands if taken before meals, corrosion or violent inflammation of After meals they neutralize the acids the mucous membranes of the mouth, of the gastric juice. Large amounts of esophagus, and stomach, and in marked ammonia exert a corrosive action on the irritation of the larynx and trachea, mucosae (7'. Ammonia Poisoning). owing to the penetration of ammonia Absorption and Elimination. — Con- vapor into the respiratory passages, cerning the manner in which ammonia The symptoms consist of violent pain exerts its stimulating efifect, there are in the mouth, throat, and abdomen ; sali- still differences of opinion. Some claim vation ; vomiting, sometimes bloody, that, after being rapidly absorbed, am- and, occasionally, purging. The intense monia, circulating with the blood, stim- irritation of the respiratory mucous ulates the vital centers directly; others membranes may cause, at first, a mo- believe that the centers are stimulated mentary arrest of breathing and de- mainly reflexly, as a result of the local pressed heart action, as well as spas- irritation produced in the stomach. modic contraction of the laryngeal and The researches of Magnus showed bronchial muscles. Later, the persist- ammonia to be neither absorbed nor ex- ing laryngeal irritation causes intense creted by the lungs. Hence, in so far as local burning and a characteristic dififi- its administration by inhalation is con- culty of respiration, due to actual edem- cerned, the stimulating effects of am- atous swelling of the glottis. Sudden monia would appear to be due largely death by asphyxia may result, though to peripheral sensory stimulation. more frequently it is due to shock aris- When taken internally, on the other ing from the pronounced local destruct- hand, ammonia is readily absorbed ; but ive effects of the alkali, or to collapse, on reaching the blood-stream it rapidly possibly owing to a secondary depress- undergoes a chemical change whereby ive effect of the drug on the heart and it is converted into the relatively inert medullary centers. Convulsions, how- substance urea. \\'hatever direct stim- ever, are comparatively infrequent in ulating action it may exert on the nerve- ammonia poisoning, and this fact would centers and heart is, therefore, quickly tend to indicate that in the majority of brought to an end. cases the amount of ammonia absorbed By the conversion into urea, the am- is insufficient to cause violent direct ef- monium in ammonium hydroxide loses fects on the nerve-centers, the characteristics of an alkali metal. The ultimate results in cases of am- For this reason ammonia does not in- monia poisoning can seldom be pre- crease the alkalinity of the body fluids, dieted with certainty. Not only may differing thus from the hydroxides of laryngeal or bronchial inflammation fol- sodium and potassium, which cannot low, but the gastric mucosa may be so undergo the change referred to. greatly injured as permanently to im- The urea produced from the ammo- pair the functions of the stomach, and nia is naturally eliminated largely with even cause death from inanition. More- the urine, which may be somewhat in- over, in cases that recover from the creased in amount owing to stimulation acute effects, stricture of the esophagus of the renal cells by the excess of urea. is a frequent sequela. As with other AMMONIA (SAJOUS). 535 caustics, the upper and lower extremi- be treated by dilatation with bougies ties of the gullet and the point at which {v. Esophagus, Stricture of), it crosses the left bronchus are the fa- APPLIED THERAPEUTICS OF vorite seats of corrosion. AMMONIA. — As a Stimulant. — Am- Large doses of ammonia (providing monia is of great value as a rapidly a sufficient amount is absorbed) are said acting "diffusible" stimulant, exerting to diminish the oxygen-absorbing power a marked beneficial effect in all forms of the red blood-corpuscles and to inter- of acute circulatory, respiratory, and fere with coagidation. nervous depression. It may be admin- Treatment of Ammonia Poisoning, istered either by the mouth, by inhala- — The chief ends to be sought in the tion, or by hypodermic or intravenous treatment of the first stage of the poison- injection. For internal use, the arc- ing are neutralization, dilution, and re- matic spirit of ammonia, always well moval of the obnoxious agent. Vine- diluted, in doses of 15 minims to 1 gar, lemon juice, or any other avail- dram (1 to 4 c.c), is the best prep- able acid (preferably a vegetable aration. For inhalation, ordinary am- acid), well diluted, should be given, monia w^ater, or "smelling salts," may together with a large amount of be used. The effect of ammonia, when water. \\'here no acid is at hand, an it is taken internally, is believed by oil, such as olive oil or linseed oil, some to be chiefly reflex, varying in forms the best substitute. The stom- intensity with the degree of local irrita- ach-pump may then be cautiously tion produced. A similar mode of ac- used, though, if sufficient time for tion is known to obtain when ammonia marked corrosion of the tissues has al- is inhaled; none of it is absorbed ready elapsed, its passage is attended through the lungs, and the effect is cor- with some danger, owing to the liability respondingly fugacious. The true stim- of the weakened tissues to perforation. ulating eft'ect of ammonia is best ob- Morphine should be given if the tained by intravenous injection, though pain is severe, and tracheotomy may the hypodermic method is oftener em- be required if asphyxia threatens. ployed. If symptoms of shock or secondary In asphyxia, whatever be its origin, collapse appear, the usual measures for ammonia is a valuable agent. It may, combating these states — hypodermic with advantage, be given at once inter- injections of ether, digitalis, atropine, nally and by inhalation. During the strychnine; hot, strong coffee by the latter procedure care should be taken rectum ; external heat, artificial respi- not to spill any of the strong liquid into ration, etc. — should be availed of. the patient's mouth or nose, — an acci- Demulcents, such as olive oil, starch dent which is likely to occur when the paste, tragacanth mucilage, milk, patient is recumbent, and which is apt white of egg, or an infusion of elm to yield a more pronounced effect, how- bark, should be freely administered ever, than its ingestion, to soothe the inflamed mucous mem- In cases of sudden heart-failure or branes. No food is to be given by collapse, as may result from the pres- the mouth for two days after the ence of bacterial toxins or poisoning accident. by depressant drugs, such as hydro- Strictures of the esophagus should cyanic acid, chloroform, chloral by- 586 AMMONIA (SAJOUS). drate, aconite, etc., repeated ingestion of 15 minims to 1 dram of the aro- matic spirit of ammonia, diluted with half a tumblerful of water, or the in- travenous injection of like amounts of ammonia water, diluted with 6 drams of sterile water, will usually exert a powerful stimulating action. Ammo- nia may likewise be used internally to combat the effects of bites of poison- ous animals. In ordinary "fainting" and the lighter forms of shock, the inhalation of ammonia from its solution or from smelling salts may suffice to bring about the desired result. Tn infants, collapse occurring in summer diarrhea may be combated with occasional doses of a few drops of am- monia, well diluted. For the algid stage of cholera, am- monia internally and ether hypoder- mically, with simultaneous free admin- istration of alcohol, have been highly recommended by Giacich. Marked im- provement in the general condition was noted within two hours after the insti- tution of this mode of treatment, and over 50 per cent, of cases already in the algid stage are said to have recov- ered. In acute alcoholic intoxication, the ammonia preparations are consider- ably used. Lavage of the stomach, followed by the administration of 10 drops of ammonia water in a half-tum- blerful of water, will often counteract promptly the effects of the alcohol. Ammonia has also been used with benefit in the treatment of delirium tremens (Butler). As an Antacid. — Internally, am- monia may be used to counteract gastric hyperacidity, indicated by such symptoms as acid eructations ("heartburn") and flatulence. Par- ticularly where there are pronounced abnormal fermentative processes, re- sulting in the formation of vegetable acids, does ammonia appear to be effi- cient. A few drops (3 to 5) of the water of ammonia, or 10 drops of the aromatic spirit, well diluted, will often give relief under these circumstances. It should be remembered that, al- though the ammonia introduced will tend to neutralize any acids present, the local irritation produced by it will, in addition, tend to stimulate the gas- tric glands and musculature. Hence the special degree of benefit obtained where there is flatulence and in cases where the gastric functions are weak- ened by general debility or excessive alcoholic indulgence. In poisoning by mineral acids, such as hydrochloric or sulphuric acids, well- diluted ammonia may be given as an antidote (though a less-irritating alkali, when at hand, is much preferable). Externally, in painful insect bites, ammonia may be used to neutralize the acid (frequently formic acid) intro- duced at the moment of stinging. Its antiseptic action is also helpful. As a Counterirritant, Rubefacient, or Cauterant. — Ammonia water ap- plied to the skin acts powerfully in re- lieving subjacent pain, though the su- perficial pain attending its use is not infrequently more severe than is the case with other counterirritants. In patients with kidney aifections, in particular, it has been used as a vesi- cant in place of cantharides, which causes harmful renal irritation in these cases. It has the property of passing through the horny layer of the epider- mis without destroying it (as would other strong alkalies), and of inducing blister formation through irritation of the dermis. AMMONIUM (SAJOUS). 587 In bruises, chilblains, and other su- perficial lesions, ammonia liniment may be employed as a rubefacient. It sometimes relieves the milder forms of chronic rheumatism, inckiding the joint manifestations and lumbago. The corrosive and antiseptic prop- erties of ammonia may be utilized with great advantage and convenience in treatingf the bites of carnivorous animals, venomous reptiles and in- sects. In snake-bites, for example, strong ammonia water may be applied directly to the wound, the general stimulating effect of ammonia being also availed of by giving an intraven- ous injection of 30 to 60 minims of the weaker solution in 6 drams of sterile water. In insect stings, the local ap- plication of ammonia water will often greatly reduce the pain or itching; es- pecially where a tendency to local in- fection exists, the antiseptic property of the remedy may be utilized with great benefit. The patient should al- ways be cautioned, however, to remove the ammonia when marked redness of the skin appears ; otherwise, consider- able local injury is likely to result. In a case witnessed by the writers, the pa- tient had used it in the form of a com- press to treat a horse-fly bite. The large area thus "treated" resembled a burn of the second degree. Most people handle ammonia carelessly. In the "hair tonics" recommended in premature alopecia, ammonia wa- ter is considered a valuable ingre- dient. The aromatic spirit of am- monia is also used in various other affections of the scalp, including pityriasis, etc. C. E. DE^I. Sajous AND L. T. DE M. Sajous, Philadelphia. AMMONIUM. —A metal-like body, never yet isolated in pure form, but known, from the manner in which its compounds can be formed by the in- teraction of ammonia gas and acids, to have the chemical composition NH4. The compounds of ammonium greatly resemble those of potassium; hence the inclusion of ammonium in the group of alkali metals. The official salts of am- monium are the following: — Aninionii ben::oas (ammonium ben- zoate) ; dose, 5 to 30 grains (0.3 to 2.0 grams). Ammonii hromidum (ammonium bro- mide) ; dose, 5 to 30 grains (0.3 to 2.0 grams). Ammonii carbonas (ammonium car- bonate) ; dose, 2 to 15 grains (0.12 to 1.0 gram). Amvionii chloridiim (ammonium chloride) ; dose, 2 to 30 grains (0.12 to 2.0 grams). Ammonii iodiditm (ammonium io- dide) ; dose, 3 to 15 grains (0.2 to 1.0 gram). Ammonii salicylas (ammonium sali- cylate) ; dose, 3 to 15 grains (0.2 to 1.0 gram). Ammonii valeras (ammonium vale- rianate or valerate) ; dose, 2 to 10 grains (0.12 to 0.6 gram). Ammonium acetate is ofificial in liquor ammonii acctatis (spirit of Min- dererus), a solution of diluted acetic acid nearly saturated with ammo- nium carbonate ; dose, 4 fluidrams (16 c.c, containing about 15 grains or 1 gram of ammonium acetate), and in liquor ferri et ammonii acetatis (Basham's mixture), which is made up of tincture of ferric chloride, 1 fluidram (4 c.c.) ; diluted acetic acid, 1% fluidrams (6 c.c.) ; solution of ammonium acetate, 12^4 fluidrams (50 c.c.) ; aromatic elixir, 3 fluidrams 588 AMMONIUM (SAJOUS). (12 c.c.)', glycerin, 3 fluidrams (12 c.c), and water, enough to make 25 fluidrams (100 c.c.) ; dose, 4 fluidrams (16 c.c). PHYSIOLOGICAL ACTION.— The effects of the compounds of am- monium are a composite of those of the ammonium group or ion itself, and of the acid group in union with it. The latter may not only modify that of the ammonium, as in ammonium bro- mide, but may completely overshadow it, as in ammonium arsenate. The effects of the ammonium ion, when it enters the circulation, are, in general, those of a promptly acting, but fleeting stimulant. Tf the amount in- troduced be excessive, depression may follow the primary stimulation. In the nervous system the stimulat- ing effects of ammonium bear chiefly upon the spinal cord and medulla. The motor spinal centers are excited to in- creased activity, exaggerated reflex ac- tion, and even convulsions, being among the most evident results. The cere- brum, however, is, if anything, de- pressed rather than stimulated. The circulation is influenced in various ways: 1. Stimulation of the vaso- motor center in the medulla causes a rise of blood-pressure through constriction of the peripheral blood- vessels. 2. The heart muscle is directly stimulated, the result being a strengthening of its beats and further rise in the blood-pressure. 3. Excitation of the vagus (inhibitory) center in the medulla may cause some slowing in the heart rate. Respiration is accelerated and deepened through stimulation of the medullary centers presiding over this function. The body secretions, especially the sweat, saliva, and mucous secretions of the alimen- tary and respiratory tracts, are in- creased by ammonium, partly through stimulation of the nervous centers gov- erning secretory processes (exclusively so in case of the sweat secretion), and partly owing to local effects on the se- creting cells. Though most of the ammonium com- pounds are readily and promptly ab- sorbed from the stomach and intestines, their excretion through the urine and other secreted fluids is so rapid as to greatly limit the power and duration of their effects when taken by the mouth. Further, certain of the salts of ammo- nium, i.e., the acetate and citrate, when absorbed, are oxidized to ammonium carbonate in the system, and this, in turn, undergoes a rapid decomposition, probably mainly in the liver, whereby it is converted into urea. The ammo- nium group is thus destroyed, and its specific effects promptly disappear. Only by intravenous injection of rather considerable amounts of ammonium salts are the effects of the NH4 group obtained with any degree of intensity. The decomposition of the NH4 group into urea involves loss of the alkaline properties of its compounds. For this reason the alkalinity of the blood is not increased and the acidity of the urine not diminished by the administration of alkaline salts of ammonium, as they would be by giving alkaline salts of so- dium and potassium. Ammonium salts which are not changed to the carbonate and elimi- nated as urea — e.g., ammonium chlo- ride— are excreted as neutral salts, and, therefore, also fail to influence the re- action of the urine. The contrast between the stimulating action of ammonium hydroxide (am- monia) or ammonium carbonate and the almost complete absence of it in the case of ammonium chloride is now be- AMMONIUM (;SAJOUS). 589 lieved to be due not to any greater ra- pidity of absorption or more prolonged persistence of ammonium in the blood (the reverse being, in reality, the case), but to the reflex stimulation caused by the caustic alkaline action of the first- mentioned two compounds on the gas- tric mucosa (or wherever else brought into relation with the organism), as compared to the low degree of local ir- ritation caused by the practically neu- tral chloride of ammonium. As already mentioned, some of the ammonium compounds owe their therapeutic value chiefly to the acid group — benzoate, bromide, salicylate, etc. — with which the ammonium is in combination. For information con- cerning these the reader is referred to the headings under which the respect- ive acids are considered : Benzoic acid, bromides, salicylic acid, etc. The more important of the compounds in the physiological action of which the ammonium group plays the leading part will be treated of in the following sections. AMMONIUM ACETATE.— Am- monium acetate (CH3. COONH4) oc- curs as a white crystalline solid, freely soluble in water. It is seldom used in its natural state, but enters into the composition of the official liquor am- monii acctatis (spirit of mindererus), which is extensively employed. This fluid is prepared by neutralizing dilute acetic acid with ammonium carbonate (5 grams of the former in 100 c.c. of the latter, according to pharmacopeial directions), the result being a colorless liquid, which may give off a faint odor of acetic acid, and has a mildly saline, acidulous taste and an acid reaction. The preparation is required to contain not less than 7 per cent, of ammonium acetate, and should be freshly prepared when wanted. The dose of spirit of mindererus is 2 fluidrams to 1 ounce (8.0 to 30.0 c.c), repeated every two or three hours. Liquor fcrri ct ammonii acetatis (Basham's mixture) will be considered among the preparations of iron. MODE OF ADMINISTRATION. — Liquor ammonii acetatis is best ad- ministered well diluted in sweetened water. Sparkling water (charged with carbon dioxide) is also advantageous as a diluent. INCOMPATIBLES. — Strong acids, which enter in combination with the ammonium, replacing the weaker acetate radical ; compounds of- bases stronger than ammonium (sodium, po- tassium), with acids weaker than acetic acid, e.g., the carbonates of sodium and potassium; lime water (calcium hy- droxide) ; metallic salts, such as those of silver and lead. PHYSIOLOGICAL ACTION.— Ammonium acetate, especially when given in the official solution, is the most strongly diaphoretic of the salts of am- monium. Its action is believed to take place largely, if not solely, through stimulation of the sweat-center. The diaphoresis occurring under its influ- ence is greatly assisted if the cutaneous vessels are already in a state of dilata- tion or are caused to dilate by the ap- plication of warmth — blankets — to the patient's skin, or by combination with sweet spirit of niter or aconite. A second useful property of this salt is its action as a diuretic. This ac- tion is exerted most strongly when diaphoresis is held in abeyance, i.e., when the skin vessels are not dilated. The diuretic effect of ammonium ace- tate is not produced through irritation of the kidney-cells. This is one of the ammonium salts which are rapidly con- 590 AMMONIUM (SAJOUS). verted in the system, first into ammo- nium carbonate, then into urea ; hence the diuretic effect is probably chiefly that of urea, — a normal stimulant to the renal function. Ammonium acetate is believed to be one of the most rapidly absorbed of the ammonium salts; we should, therefore, expect that some of the stimulating ac- tion of ammonium on the medullary nerve-centers and circulation would be exerted on ingestion of this salt. Such stimulation does not, however, with the exception of the sweat-center, appear to occur to any marked extent. The reason for the special preponderance of diaphoresis in the action of this salt of ammonium is not definitely known. THERAPEUTICS.— As a Diapho- retic and Diuretic. — The solution of ammonium acetate is useful as a mild sweat-producer and diuretic in febrile diseases, including acute coryza, in- fluenza, mumps, the eruptive diseases of childhood, etc. The elimination of toxic products, in wdiich the skin, as well as the kidneys, plays so important a part in these affections, is hastened by it. It also tends to reduce excess- ive temperatures by increasing the amount of fluid evaporated from the skin. In tiie diseases of childhood, when the eruption is delayed, am- monium acetate will favor its ap- pearance. It has also been found serviceable in muscular rheumatism (Butler). In acute alcoholic intoxication am- monium acetate has been found to re- move promptly the symptoms. In migraine, too, through some obscure mode of action, and in amenorrhea, the remedy has sometimes proved beneficial (Butler). Externally, solutions of ammonium acetate have been applied as a lotion over contusions, beginning abscesses and glandular enlargements, and cer- tain skin fliscases, e.g., prurigo. In chronic ophthalmic inflammations, also, it has been used as an eye-wash, a little laudanum being added to the acetate solution in order to relieve local discomfort. AMMONIUM CARBONATE.— The substance used under this name is not the pure car])onate of ammonium, (NI 14)2003, but is a mixture in va- riable ratio of acid ammonium bicar- bonate, (NH4)HCO... or CO(OH)- ONH4, and ammonium carbamate, CO- (NH2)Oi\H4. This mixture is also known as ammonium sesquicarbonate, hartshorn, sal volatile, Preston salts, or bakers' ammonia. It is made by heat- ing an ammonium salt, such as the chlo- ride, with chalk (calcium carbonate), and occurs in white, hard, translucent masses having a sharp, saline taste, a strong odor of ammonia, and a strongly alkaline reaction to litmus. It loses both ammonia gas and carbon dioxide when exposed to the air, and effloresces, becoming opaque and friable. When heated it volatilizes completely. When dissolved in hot water it is decomposed, ammonia and carbon dioxide being driven off; upon further boiling it dis- appears from the solution by volatiliza- tion. It is soluble in 5 parts of water at a temperature of 15° C. (59° F.), and in 4 parts at 25° C. {77° ¥.). Al- cohol dissolves only its carbamate con- stituent, the acid carbonate remaining. In glycerin it is soluble to the extent of 1 in 5 parts. The purity standard set for ammonium carbonate by the United States Pharmacopoeia is that it should contain 97 per cent, of the constituents above mentioned, and should yield not less than 31.58 per cent, of ammonia gas. AMMONIUM (SAJOUS). 591 The dose of ammonii carbonas is 2 to 15 grains (0.12 to 1.0 gram), the average being 5 grains (0.3 gram). The aromatic spirit of ammonia (spiritus ammo}iies, but most marked in the posterior lateral columns, as ob- served by Xonne, and to a less degree in the lateral columns. All these changes are not typical of pernicious anemia, however, and may be met with in other diseases in which cachexia and marasmus predominate, such as Addi- son's disease and diabetes. Hemor- rhagic areas in the cord and brain due to hyaline degeneration of the blood- vessels are also met wnth. \ye have seen that retinal hemorrhages consti- tute a diagnostic feature of the disease. Two cases illustrating 2 of the types of nervous-system involvement. In the first case, which had the long- er and more pronounced history of anemia, the nervous symptoms were at a minimum and the posterior col- umns of the cord, particularly in the cervical region, alone showed degen- eration, characteristically patchy in distribution. In the second case, the nervous involvement, particularly in the later stages, overshadowed the anemia. Here the spinal cord pre- ANEMIA, PERNICIOUS PROGRESSIVE (HENRY). 615 sented verj' extensive, yet incomplete degeneration with slight replacement gliosis in the posterior columns, and also a similarly irregular, but more dififuse degeneration in the lateral tracts, which, however, was a rather less complete and apparently some- what more recent process. Camac Milne (Amer. Jour. Med. Sci., Oct., 1910). The writer examined the brains of 7 persons who died of primary idio- pathic pernicious anemia. The most salient features in the pathologic anatomy of these brains, were the following: 1. Not only do degener- ated areas of the Lichtheim type, such as are typically found in the posterior and lateral funiculi of the spinal cord in pernicious anemia pa- tients, occur in the medullary por- tions of the brains of these cases, but they occur with about the same fre- quency, though their demonstration may be rendered more difficult. 2. Patients who show degenerative changes in the spinal cord at nec- ropsy, usually show the same type of lesion in the brain also. 3. In addition to these focal degenerative areas found in the white matter, which may or may not be associated with blood-vessels, one also finds a diffuse degeneration, which, though it is, as a rule, somewhat more striking in the long association tracts, also occurs in the short commissural fibers passing from one gyrus to another, thus rendering the view untenable that it is the distance of these fibers from their trophic centers which is instrumental in causing the degenera- tion. 4. The gray matter is by no means immune from the destructive process. This is usually focal in character, and begins around the pyramidal cells of the marginal gray layer, the cells themselves being ulti- mately destroyed in the process, this, in turn, giving rise to a secondary and very diffuse degeneration of the medullated fibers in the white mat- ter. 5. Though some degeneration was noted in the fibers of the inter- nal capsule and in the long tracts passing through the pons, the degen- eration at this level was less intense than that seen either in the cord or in the brain. 6. The appearance of these plaques, not only around the blood-vessels but also around some of the larger pyramidal cells, seems additional evidence that lymph stasis is an important factor in the produc- tion of these foci. 7. Well marked psychoses, such as are occasionally associated with pernicious anemia, probably have little or nothing to do with these destroyed areas. 8. The milder mental manifestations such as somnolence, apathy, and terminal delirium, are probably in a measure dependent on these lesions, though the chief causative agent of these symptoms is probably the toxin itself. Woltman (Arch, of Internal Med., June, 1918). The bone-marro\y usually presents changes which indicate abnormal activ- ity, being composed mainly, when the case is not too far advanced, of hemat- oblasts, as emphasized by Rindfl'eisch. It resembles in this state, as noted by H. C. Wood, Pineau, and others, the hemoblastic marrow of childhood. Other changes frequently found, ac- cording to Muir, are (a) increased number of nucleated red corpuscles in the marrow; (&) transformation of the fatty marrow in the shafts of the long bones into red marrow; (c) absorption of the bone trabeculse between the red inarrow. Later, it presents all the signs of excessive compensative func- tion, being actually hypertrophied in some instances. When this stage is reached the bone-marrow may lose its power to create red corpuscles. The proteids of the plasma may be altered in their respective proportions, and considerably reduced — 40 per cent, below the average normal quantity, ac- cording to Ruttan and Adami — the globulins being especially reduced. 616 ANEMIA, PERNICIOUS PROGRESSIVE (HENRY). Although fatty degeneration is pres- ent in practically all organs, emacia- tion is exceptional, though the adipose tissue is pale and yellowish, contrast- ing with the usually red muscular tis- sue. The heart, however, is enlarged and flabby, and its muscular elements are pale, friable, and fatty, its cavities containing light-colored blood. The general fatty degeneration affecting markedly the vessel walls, these are extremely friable; hence, the hemor- rhages, retinal, cutaneous, etc., and the ecchymoses so frequently witnessed. DIAGNOSIS. — While pernicious anemia j)ossesses characteristics that readily distinguish it from other blood affections. — the color of the skin, the retinal hemorrhages, etc., — the early stages are generally such as to sug- gest less dangerous diseases. Benign Anemia. — Intractability of the disease, after the removal of sup- posed causes and the faithful use of appropriate measures of treatment, strongly suggests pernicious anemia. Chlorosis. — From this affection per- nicious anemia may readily be differ- entiated by the blood examination. Instead of relative increase of hemo- globin, the presence of gigantobasts, marked oligocythemia, and macro- cytes differentiate. The erythrocytes, or red corpuscles, in chlorosis, may be normal in num- ber and size, the only change being a deficiency of hemoglobin. Again, the corpuscles may be normal in number, but diminished in size, while the per- centage of hemoglobin is normal ; finally, the corpuscles may be dimin- ished in number with either a dimin- ished, normal, or perhaps an increased percentage of hemoglobin. Leukemia. — This disease may be excluded by the absence of the char- acteristic blood-change : excess of white corpuscles. In a case of leukemia the patient often does not show enough pallor to make the physician suspect the dis- ease. The lips have a dirty-red color rather than a peculiar pallor. The number of white corpuscles would cause pallor in a patient with simple anemia, but in this disease the opacity of the blood is great and the pallor fails to show. Pseudoleukemia is excluded by the absence of the affection of the lym- phatic glands which characterizes this disease, more commonly known as Hodgkin's disease. Gastric Cancer. — This condition al- most always shows itself after the age of 40 years, whereas pernicious ane- mia is sometimes observed earlier in life. In cancer the skin is pale; in pernicious anemia the peculiar lemon color is striking in the majority of cases. While gastric symptoms and absence of hydrochloric acid are prominent features of cancer, the di- gestive disorder is slightly marked in anemia and examination of the gas- tric contents is negative. The reduc- tion of red cells is greater in perni- cious anemia than in cancer. The re- duction of hemoglobin relative to corpuscles is not so great in pernicious anemia as in cancer. The average size of red cells is greater and poly- chromatophilia is marked. In grave anemia in 11 cases of nephritis with uremia, the anemia masked the renal disease. The ane- mia seems usually the result of the uremia and fluctuates with it. Cases of pernicious anemia may be mis- taken for arteriosclerosis. In doubt- ful cases of arteriosclerosis, espccially those with a historj^ of remissions, frequent blood counts and neurologic examinations for cord changes should ANEMIA, PERNICIOUS PROGRESSIVE (HENRY). 617 be routine procedures. Aubertin and Yacoel (Presse med., July 10, 1920). [It should not be forgotten that the causative toxemia in nephritis, arterio- sclerosis, and other conditions may like- wise produce through hemolysis all the symptoms of pernicious anemia. S.] Finally, increasing emaciation at- tends a cancerous disorder, whereas in cases of pernicious anemia the pa- tient not only retains his adipose tis- sues, but sometimes becomes corpu- lent. In rare cases, however, there has been extreme emaciation. The pernicious anemia of infants — a rare condition — is recognized, ac- cording to Rotch and Ladd, through the following diagnostic points : The insidious onset with moderate and paroxysmal attacks of indigestion, the extreme pallor, great loss of strength, slightly elevated temperature for months, and absence of glandular or splenic enlargements or of any demon- strable cause for a secondary anemia. The signs which are almost pathogno- monic in adults lose significance, on account of the greater instability of the infant's blood-makingf function. Alegaloblasts, normoblasts, macro- cytes, and poikilocytes mav occur in grave anemias other than "pernicious," yet are needed for diagnosis. ETIOLOGY.— The ^ main patho- genic factor, hemolysis, has been re- viewed under a preceding heading ; we still have to consider, however, the conditions which either predispose to the disease or are capable of causing it. As to predisposing agencies, al- though the disease occasionally occurs in children and young adults, it is most common at about the age of 40 years. Males are attacked more fre- quently than females, with a slight difiference in favor of the former. The disease is more prevalent among the better than in the lower classes, and is most common in Europe, especially in Switzerland, e.g., in regions in which the people are badly fed and live in poorly ventilated and badly lighted houses. Fright and grief are prominent etiological factors. Syph- ilis, sarcoma, and other disorders cap- able of impairing hematopoietic func- tions of the bones are also capable of bringing on the disease. According to Grawitz, the following group of etiological factors has been established: 1. Gastrointestinal dis- ease of long standing, poor food, im- paired digestion ; chronic constipation, especially in women frequently preg- nant ; irregular defecation in women and girls, especially those of hysteri- cal temperament. In such cases it is due to intoxication from the gastroin- testinal tract. 2. Pregnancy. Here, too, probably, there is an autointoxi- cation from the intestinal tract, on ac- count of pressure exerted-by the gravid uterus on the bowel. 3. Chronic hem- orrhages, especially of small size. 4. Constitutional syphilis, particularly when associated with sclerosis of the marrow of the long bones. 5. Bad hygienic conditions of various kinds, especially in the female sex ; hard work, with instifficient food, bad air, and emotional excitement. In higher social strata the disease may be found in women who are subjected to intense mental strain as the result of a desire to equal men in physical efforts. Fre- quent preg'nancy and prolonged lacta- tion are also factors. 6. Chronic poi- soning, as, e.g., by carbon monoxide. 7. Bothriocephalus and ankylostomum — those cases belong here that are not cured after the expulsion of the worms. Pernicious anemia is not a specific entity, but a clinical syndrome of 618 ANEMIA, PERNICIOUS PROGRESSIVE (HENRY). varying etiology. Etiologically, the disease can be considered as crypto- genetic, or of concealed origin. Under the former the writers group: (1) repeated hemorrhage (gastric, uterine, nasal, and vesical); (2) intes- tinal parasites (bothriocephalus and ankylostoma); (3) malaria; (4) bac- terial infections; (5) tuberculosis; (6) syphilis; (7) cancer, especially gastric; (8) gastrointestinal disor- ders and autointoxications, which are said to be the cause of the so-called idiopathic cases; (9) nephritis; (10) pregnancy; (11) lead; (12) carbon monoxide, arsenic, and opium. The factors necessary for any of the above conditions to result, in this syndrome are («) an excessive inten- sity of the morbid cause; (b) the localization of the infection; (f) the duration or repetition of the cause; (d) an accumulation of the morbid condition; (c) predisposition. On the whole, progressive pernicious ane- mia can be the final stage of second- ary anemias. Ladd and Salomon (Revue de med., April and May, 1908). Three cases of severe anemia wit- nessed due to repeated small bleed- ings and occasionally larger ones from varicosities situated 10 to 15 cm. above the anus which could easily be seen with the proctoscope. Destruction of these varicosities by the Paquelin cautery rapidly cured the anemia. C. A. Ewald (Berl. klin. Woch., Jan. 9, 1911). Pregnant women represent the larg- est proportion of cases. Repeated par- turition is probably the most prolific cause of the disease, for it is seldom met with in primiparae. Excessive and prolonged lactation and puerperal hem- orrhages and other exhausting condi- tions frequently appear as the primary element in the causation of the disease. Two cases of severe anemia in pregnant women in which marked improvement followed delivery in 1 case, and by the return of the ane- mia at each pregnancy in the other case. Weidenmann (Corresp. blatt f. Schweizer Aerzte, May 25, 1918). Anemias which are met with dur- ing pregnancy differ from true per- nicious anemia and seem to owe their origin to the pregnancy itself. The first symptoms are scarcely ob- served before the second half of pregnancy. After labor it most fre- quently undergoes a rapid aggrava- tion, but in some cases it clears up. The prognosis is very grave, and medical treatment is generally in- effective. E. Petersen (Arch. mens, d'obstet. et de gynec, vii, 1, 1918). In reporting a case the writer states that a review of the literature leads very directly to the conclusion that pregnancy and the puerperium favor the development and hasten the course of pernicious anemia. While pernicious anemia is not a disease peculiar to pregnancy it is neverthe- less true that the disease occurs with unusual frequency in the course of pregnancy and the puerperium. Just what the predisposing factors are in pregnancy is not known. Prolonged lactation, frequent child-bearing, the toxemias of pregnancy, and unfavoi-- able hygienic surroundings are fac- tors to be reckoned with but are not conclusive. P. Findley (Trans. Amer. Gynec. Soc, May, 1918). Certain atrophic conditions of the gastric mucous membrane, ulcers of the stomach, malaria, syphilis, cancer, and alcoholism have also been consid- ered as etiological factors. Pyorrhea alveolaris and carious teeth are increasingly asserting their role as sources of toxins which promote the disease. Contrary to the prevailing belief and the assertions of Ehrlich and Lazarus, pernicious anemia may be a family disease. Series of cases which all occurred in the same family — all fatal — in 2 brothers, 1 sister, a paternal cousin and a paternal uncle. Blood exami- nations made in all established the ANEMIA, PERNICIOUS PROGRESSIVE (HENRY). 619 diagnosis beyond a doubt. Patek (Jour. Anier. Med. Assoc, Mar. 6, 1911). The writer observed 5 instances in one family, the father, mother, and 3 sons. C. J. Bartlett (Jour. Amer. Med. Assoc, Jan. 18, 1913). PROGNOSIS.— The disease as a rule ends fatally and in no given case can a favorable prognosis be given. It is true that under arsenic and other measures recoveries take place, many of which last over a period of years. Relapses, however, are to be expected. About one-half of the fatal cases last from one to six months; the re- maining seldom reach beyond the sec- ond year. Periods of transitory im- provement of varying duration are often a part of the natural course of the disease; so that too much impor- tance must not be attached to the favor- able results that may follow the special line of medication employed. Even if such improvement continues for a long time, the conclusion must not be too hastily reached that the disease is cured. According to Goodall, the prog- nosis may to a certain extent be based upon certain characteristics of the course of the blood-picture : — 1. Acute Favorable Cases. — In these the symptoms are marked ; the red cells are much diminished, but show a tend- ency to rise; the megaloblasts are atyp- ical and not numerous ; the normoblasts are numerous ; the color index is high, but tends to fall; the polychromato- philia is not marked ; the percentage of polymorphonuclear cells is high; the myelocytes are absent or scanty. Course. — A remission to a fairly normal condition may occur, which may be maintained for years. 2. Chronic Cases. — In these the symptoms are not well marked ; the red cells tend to remain about one or two million ; the megaloblasts are absent or scanty ; the normoblasts are absent or scanty ; the color index is generally low; the polychromatophilia is slight; the percentage of lymphocytes is high; the myelocytes are scanty. Course. — The cases are apt to be chronic. The patients can work, though they feel weak, and, though febrile attacks, etc., may occur, they have little bad effect. Improvement seldom occurs, but the duration may be for several years. 3. Subacute Cases. — In these the symptoms are fairly well marked ; the red cells about one million, showing slow and irregular tendency to rise ; the megaloblasts are numerous ; the normo- blasts are less numerous than megalo- blasts ; the color index is high ; the polychromatophilia is distinct ; the per- centage of lymphocytes is high in the absence of fever; the myelocytes are fairly numerous. Course. — Symptoms improve ; blood improves to a certain extent. The duration is about two years, unless com- plications reduce this period. 4. Acute Unfavorable Cases. — In this type the symptoms are marked, and there may be hemorrhages ; the red cells are about one million, and tend to remain or go lower; the megaloblasts are typical and numerous; the normo- blasts are less numerous than megalo- blasts ; the color index is high ; the polychromatophilia is marked ; the per- centage of lymphocytes is high in the absence of fever ; the myelocytes may be numerous. Course. — A fatal termination is to be expected in a few months. The tendency to relapse is in re- ality due to the remarkable persist- ence of the specific hemolytic infec- tion underlying the disease, since it 620 ANEMIA, PERNICIOUS PROGRESSIVE (HENRY). is always accompanied by a recru- descence of the lesions in the tongue, stomach, or intestine, and by the glossitic, gastric, or intestinal symp- toms connected therewith. Hunter (Brit. Med. Jour., Nov. 9, 1907). The immediate prognosis in certain cases of pernicious anemia with blood depletion below 400,000, although serious, is not hopeless. The prog- nosis depends on the degree of red- cell regeneration in the bone-marrow; the age of the individual and the potency of the hemolytic poison be- ing important factors. Stone (Jour. Amer. Med. Assoc, April 18, 1908). Report of 3 cases of pernicious anemia with remissions, with tabu- lated blood-counts. In one case the improvement followed the removal of the patient from the county farm to the hospital, where the better hy- gienic and dietary conditions were undoul)tedly a strong factor. In sev- eral cases observed, out of a total of 25 in the last two and a half years, in which fermentative changes in the intestines were a prominent symp- tom, high colonic irrigations with physiological salt solution seemed to be connected with remissions of im- provement. Tliough the blood-count shows a marked improvement in the remissions, there are still abnormal features indicating tliat a disturbance in hematogenic function still exists. At best a remission is but a partial cure, and reserve in prognosis and caution in interpreting apparent therapeutic results are always advis- able. W. L. Bierring (Jour. Amer. Med. Assoc, Aug. 1, 1908). Case of pernicious anemia in which there was a period of complete re- mission of symptoms, amounting to a cure for some sixteen years, with final relapse showing all the charac- teristic symptoms and pursuing a truly progressive course to a fatal ending. A. McPhedran (Amer. Jour. Med. Sci., Aug., 1910). Nageli has reported complete re- covery for 11 years to date in 2 cases and for 5 years in another case. Two of his patients bore other children later with no return of the anemia. The mortality is high among the chil- dren simply because anemia brings on premature delivery. Schuepbach (Correspondenzbl. f. Schweizer Aerzte, Bd. xliii, nu. 45-47, 1913). Case in a primipara. of 22 years, In whom the blood-picture was typical. As a result of a spontaneous miscar- riage she was immediately relieved of all her symptoms. The child was prematurely born, asphyxiated, and died after I'/j hours. The patient re- mained entirely free from symptoms. Wolff (Deut. med. Woch., Mar. 26, 1914). TREATMENT.— Arsenic cures the curable cases and beneiits the others. Iron is worse than useless, having shown itself injurious in several cases reported — doubtless because the liver is already overladen with iron. Fowl- er's solution may be given in 3-minim doses three times a day, increased by 1 minim daily until 30 minims are taken after each meal, provided the stomach does not rebel, which is seldom the case. The patient should be watched and the drug reduced or discontinued temi)orarily on the appearance of any of the physiological effects of arsenic: edema of the lids, etc. In some in- stances the doses have been increased with inarked benefit until as much as 20 drops were taken at a dose. The cause of the hemolysis must be carefully sought and removed. It is be- cause this phase of the treatment of the disease is often overlooked that its prognosis is so unfavorable. Considerable importance is at- tached by the writer to oral sepsis, particularly that known to underlie various disorders of toxemic origin, pyorrhea alveolaris. Carious teeth should be removed, and, if there is pyorrhea alveolaris, the affected teeth taken out; if the patient's condition ANEMIA, PERNICIOUS PROGRESSIVE (HENRY). 621 does not permit, local antiseptic treatment, together with an autogen- ous vaccine, may be tried. W. H. Wilcox (Pract., Sept., 1913). [In the article on Riggs*s Disease, pyor- rhea alveolaris. in the eighth volume, will be found other efficient methods for the prevention of toxemia due to this cause. S.] The writers recommend removal of all ascertainable foci of infection, an abundant roborant diet, arsenical treatment, the administration of hy- drochloric acid immediately after meals, and of pancreatin and calcium carbonate 3 hours after each meal. Splenectomy and transfusions of blood were not found necessary. Several of the patients thus treated have remained well over a long period. L. F. Barker and T. P. Sprunt (Trans. Amer. Med. Assoc; X. Y. Med. Jour., June 9, 1917). The writer had 24 cases in which operations to eliminate pathogenic foci had been resorted to. The regions in which the foci were found were the gall-bladder, the appendix, and the mouth and throat. Of the 24 cases, 14, or 58 per cent., were all clinically in good condition after in- tervals since operation varying from about 7 to 32 months. This latter case is perfectly well and carries no evidence of pernicious anemia in her blood, except an occasional normo- blast. In all cases except one in which the disease has recurred, the patient presented mental, nervous or spinal cord symptoms when they came under treatment, and in most of them these symptoms occurred early in the disease. It would seem that in all cases with involvement of the spinal cord and central nervous system, the prognosis is extremely bad under any form of treatment. Such patients should not be submit- ted to operation. Percy (Surg., Gynec. and Obstet., May, 1917). According to Grawitz, rest in bed is one of the first requisites; the assimi- lation of food must be stimulated. The patient should be placed on a milk and vec,^ctahle diet. Lavage of the stom- ach, intestinal irrigation, and saline laxatives are useful. If the urine con- tains much indican intestinal antisep- tics are indicated. He also regards arsenic as the best remedy ; it can be given with quinine. Inhalations of oxygen have been employed with ad- vantage. Massage and gymnastic ex- ercises are often of service. After apparent recovery the patient must be carefully watched, as relapses may oc- cur, particularly if the hygienic and dietetic conditions are unfavorable. Case of pernicious anemia treated by Grawitz's method. The patient was a man 33 years old who was ad- mitted to the hospital after suffering for five weeks from anemia and weakness. All the symptoms mani- fested by the patient. were that of a typical case of pernicious anemia. Treatment consisted of a strict diet of milk and vegetables, daily ene- mata, with arsenic and hydrochloric acid given by the mouth. Lavage of the stomach was not performed, owing to the patient's objections. After eight weeks in the hospital and a month's holiday in the mountains his general condition was excellent. Nicolayson (Lancet, Nov. 7, 1908). During overfeeding, symptomatic improvement took place with distinct betterment in the blood picture in 3 cases observed by the writer. A diet allowing from 60 to 65 calories per kilogram (approximately double the minimum requirement) is recom- mended, this to be given in the ratio of protein, 16 per cent; fat, 42 per cent., and carbohydrates, 42 per cent. Peppard (Minn. Med., Sept., 1919). When the gastric disorder, which is a usual symptom, prevents the ad- ministration of arsenic, the latter may be given subcutaneously, while the stomach is treated directly by lavage. Or, salvarsan or neosalvarsan might be tried. 622 ANEMIA, PERNICIOUS PROGRESSIVE (HENRY). In 1 of several cases in which sal- varsan proved effective, the patient had no history of syphilis, and gave a negative Wassermann in the serum and spinal fluid before the salvarsan was given. And yet this patient, who was in his fifth relapse, quite unre- sponsive to Fowler's solution and only showed a very slight improve- ment after four months of sodium cacodylate injections, showed after the intravenous administration of salvarsan, in doses of 0.3 Gm. (5 grains), every 4 weeks, a steady rise in the blood-count. The red cells, in 16 weeks, rose from 500,000 to 5,- 000,000, the hemoglobin from 23 per cent, to 90 per cent., and the patient's general condition was much im- proved. It is evident that it is as a powerful arsenical preparation, i.e., as arsenobenzol. that salvarsan acts, and that as such it should command even greater confidence than in the past. Boggs (Bull. Johns Hopkins Hosp., xxiv, 322, 1913). In a case of pernicious anemia with achylia gastrica refractory to Fow- ler's solution, symptomatic recovery occurred under a single intravenous injection of salvarsan. The patient gained 30 pounds in weight with a return of the blood-picture to nor- mal, but a positive Wassermann re- mained in the serum and negative in the spinal fluid. It is not. therefore, as an antiluetic that salvarsan acts. W. Egbert Rol)ertson (X. Y. Med. Jour.. July 4, 1914). It Ijecomes a question whether neo- salvarsan might not be preferable to salvarsan in these cases, and whether either is preferable to arsenic. The writer used small doses of salvarsan and neosalvarsan intramuscularly in 21 cases. The benefit was more prompt and the duration of the im- provement generallj' longer than when arsenic was given by the mouth. There also seemed to be a larger proportion of apparent cures. There was usually slight local dis- turbance and some fever. Morphine was occasionally necessary when the pain was very troublesome. Salvar- san seemed more effective than neo- salvarsan, Imt tlie latter caused less local reaction. Bramwell (Brit. Med. Jour., Mar. 6, 1915). The rate of salvarsan given intra- venously in pernicious anemia was shown bv the writer's experiences in 3 very severe cases. In all of them the alministration of small doses of sal- varsan was followed by restoration of the blood-picture almost to nor- mal, but 2 of the cases recurred later, 1 with a fatal outcome. Lampe (Med. Klinik, Nov. 19, 1916). An excess of hydrochloric acid is not uncommonly found in the gastric se- cretions. In such cases See recom- mends an almost exclusive diet of meat and other albuminous foods: raw meat to the extent of 10 to 12 ounces daily. In the majority of cases there is deficiency of hydrochloric acid and pepsin, especially in advanced cases. Good effects have been obtained from lari^e doses of hydrochloric acid and pepsin under these conditions. The great majority of cases of per- nicious anemia suffer from an ab- sence of hydrochloric acid and pep- sin in the gastric secretion, and this condition is further harmful in that the essential element for pancreatic secretion is produced only under the stimulus of the acid chj'me passing over the duodenal mucosa. To cause an artificial digestion, pancreatic as well a§ gastric, hydrochloric acid and pepsin in much larger doses than are usually considered permissible prove effective. In a personal case, the pa- tient received 30 grains of pepsin and 105 minims of dilute hydrochloric acid three times a day, the latter be- ing given in 15-minim doses every ten minutes in albumin water to dis- guise the taste. The fact that the acid was given combined instead of free did not affect its action. The further treatment consisted in daily irrigations of the colon and a liberal mixed diet. It was shown from the ANEMIA, PERNICIOUS PROGRESSIVE (HENRY). 623 blood examination that the treatment had been followed by most satisfac- tory results. Julius Rudisch (Med. Rec., March 5, 1910). Croftan, of Chicago, found that 15 drops of the strong hydrochloric acid after each meal procured notable im- provement in 14 cases, the symptoms of pernicious anemia disappearing while those of achylia persisted. The writer recommends Croftan's treat- ment in all cases showing reduced gastric aciditj^. He gives 10 to 15 drops of the acid in mucilage water a few minutes after each meal, the dose being repeated in 30 minutes. The mucilage water, which is em- ployed to prevent injury to the gas- tric mucosa by the acid, consists of 1 ounce (30 Cm.) of pulverized acacia to 1 quart (1000 c.c.) of water. One- half glassful of the mucilage water is used to each dose of acid. He deems it important to regulate care- fully the dose, for if too little is given the patient will not reap the benefit of the treatment, while if too much is given he will not retain the remedy. J. A. Sealy (Lancet-Clinic, Feb. 15, 1913). The use of bone-marrow, intro- duced by Fraser, has given good re- sults in some cases and no results whatever in others. Freshly prepared each day with an equal quantity of glycerin, red marrow, 1 or 2 ounces daily, has seemed to give the best re- sults. It should be tried only where arsenic has failed. Transfusion of blood should never be omitted when improvement does not follow the administration of ar- senic. The best method is that em- ployed by Brakenridge, of Edin- burgh. The blood is kept fluid by admixture with one-third part of its bulk of a 1 : 20 (5 per cent.) solution of phosphate of soda in distilled water kept at blood heat. John Duncan, who performed the transfusions in Brakenridge's cases, insists upon the necessity of slowness in operating. He regards thirty minutes as the minimum time that should be occu- pied in injecting 8 ounces of fluid. Series of 26 cases treated by trans- fusion at the Mayo Clinic. Forty- six transfusions were performed in the series, a single transfusion prov- ing sufficient in only 11 patients. Sixty-nine per cent, of the entire series received marked immediate benefit from the procedure. Among 14 unfavorable cases deemed unsuit- able for splenectomy similar improve- ment was noted in 50 per cent. Up to the sixth decade, the age of the patient had no bearing on the results; of 5 patients between 60 and 70 but 1 showed definite improvement. Patients with a history of remissions, even though ill for several years, seemed most benefited by transfusion. Those without remissions often failed to respond. Recent, acute cases were usually little influenced. Results fol- lowing transfusion from relatives were not superior to those in the cases of unrelated donors. But 1 patient had a severe reaction; mild fever and a severe chill lasting 40 minutes followed transfusions from the wife and from a friend; no bene- fit resulted. Eleven patients had mild fever for a day or 2. Such reactions did not prove necessarily indicative of benefit from the procedure Gen- eral improvement usually paralleled that in the hemoglobin. Distressing numbness, burning, and tingling of the hands and feet were relieved by the treatment. When no benefit fol- lows a transfusion, a diflferent donor should be tried. A. Archibald (St. Paul Med. Jour., Feb., 1917). Massive transfusions of blood offer the greatest chance of improvement to sufferers from pernicious anemia, but any error in the technique may be followed by a fatal result. The procedure is one which should be at- tem.pted only by those who have had considerable experience in intraven- ous injections and are well acquainted with the physiological teachings 624 ANEMIA, PERNICIOUS PROGRESSIVE (HENRY). about clotting of blood. Even with perfectly matched bloods reactions maj' occur, but they may be pre- vented by the administration half an hour before the injection of %5o grain (0.0004 Gm.) of hyoscine methyl bromide along with Vi; grain (0.01 Gm.) of morphine. O. Leyton (Pract., Mar. 1917). The writer observed 2 cases of per- nicious anemia in infants of 11 and 5 months from private practice. He has previously published 2 personal cases, and found 56 cases in the literature. This uicludcs 32 cases in which the anemia was traceable to the bothriocephalus or a tenia. Only 2 cases arc known of essential pro- gressive pernicious anemia in older children. The serum used was ob- tained by venesection of animals at the height of the regeneration of blood following a previous extensive withdrawal of blood. This hemato- poietic serum seems to have a de- cidedly favorable action on the com- position of the blood, when injected in cases of pernicious anemia. These infants were given daily subcutane- ous injections of 5 or 10 c.c. of the serum. The changes in the blood were from hemoglobin 20 per cent, and reds 658,875, to 53 per cent, and 2,102,125 reds in 9 months, indicate the practical efficacy of this form of serotherapy. A. D'Espine (Revue Medicale de la Suisse Romande, Aug., 1918). Transfusion offers more for pro- gressive pernicious anemia than any other form of treatment. The theory of toxic hemolysis is accepted to explain the genesis of the disease. It is highly probable that trans- fusion of blood owes its beneficial effects to the stimulation of the anti- hemolytic properties of whole blood, although the possibility of its power to increase the functional activity of the bone marrow should also be recollected. In a case seen by the writer in con- sultation transfusion produced a prompt remission lasting seven months, after the patient was thought to be lost. A second transfusion was followed by a remission, though less promptly, and at the time of writing, more than one year after the first transfusion, the patient declared that he had not "felt so well for 15 years." The blood picture, as well as the general health, were greatly improved by both transfusions. J. M. Anders (Trans. Assoc. Amer. Phys.; Mtd. Rec, Sept. 6, 1919). Daily findings reported as to the blood and urobilinemia after trans- fusion of 900 c.c. of blood drawn into 120 c.c of a 2 per cent, solution of sodium citrate in a man of ii with pernicious anemia during his third attack. In 2 weeks the erythrocytes had increased from 850,000 to 3,118,- 000; the hemoglobin from 19 to 66 per cent.; the bile pigment in the blood serum had dropped from 45 to 7, and the urobilin figure from 875 (4500 the second day after the in- fusion) to 42. The improvement pro- gressed for a time, but the man re- turned about 4 months later in his fourth attack, the erythrocytes hav- ing dropped to 1,382,000 and the hemoglobin to 28 per cent. Scheel and Bang (Norsk Mag. f. Laegev- idensk.. Mar., 1920). Defibrinated blood has been used subcutaneously by Westphalen with success. Subcutaneous injections of normal saline solution every alternate day, and on the intervening^ saline ene- mata, with arsenic internally, have been recommended bv McPhedran. Intestinal antiseptics have been rec- ommended. Hunter holds that the best intestinal antiseptic is betanaph- thol and salol, alon^ with arsenic when that can be borne. I consider thymol entitled to the first position, a fact which seems to be more fully ap- preciated in Italy than elsewhere. In accordance with the view that perni- cious anemia is due to the absorption ANEMIA, PERNICIOUS PROGRESSIVE (HENRY). 62: from the intestine of substances for- eign to the healthy body, and de- structive to the red corpuscles, its treatment by intestinal antiseptics is certainly most rational. When the disease is due to the Anky- lostoma diiodcnalc, thymol, 2 to 3 drams daily, is a very effective vermi- cide, according- to Bozzolo. Two cases clue to Bothriocephahis latus, the infection being accompanied by the severest kind of anemia. In one patient the red corpuscles fell to 780,000 and the hemoglobin to IS per cent. The second case was even more severe the red corpuscles fall- ing to 660,000 and the hemoglobin to 10 per cent. Hemorrhages were noted along the veins of the retina. The improvement in both cases after thymol treatinent was marvelous, and in the second patient in thirteen days the number of red corpuscles trebled. A. Meyer (Med. News, April 8, 1905). Herter recommends frequent and thorough irrigation of the colon, since it is the chief thriving place of the anaerobic bacteria which cause the spe- cific putrefaction. Following this sug- gestion, Dittmar and Hollis were able to report a few months ago recovery in 2 cases of pernicious anemia by irriga- tion of the colon which had resisted all other methods of treatment. In all cases of pernicious anemia, the stools should be examined to de- termine the presence of a Bacillus capsulatus aerogenes infection. If these bacteria are present in great quantities, then high irrigation, com- bined with arsenic internally, should be used; and if the patient fails to improve then the appendix offers the best route for thorough irrigation. Lucius E. Burch (Jour. Amer. Med. Assoc, March 13, 1909). When the Bacillus capsulatus a?rog- enes or the percentage of anaerobic bacteria found in evacuations from bowels is large, then, after thorough trial at colonic irrigation and failure 1—40 to improve the symptoms or to les- sen the percentage of bacteria, the operation of appendicostomy is war- ranted. J. A. Witherspoon (Southern Med. Jour., July, 1909). Cholesterin has been introduced into the therapy of pernicious anemia because of Ransom's finding that it prevented the hemolytic effects of some substances, such as saponin and cobra poison. A 3 per cent, solution of cholesterin in oil is given in 100- Gm. (3^^ ounces) doses daily. It is apt, however, to disagree with the patient. Three cases of pernicious anemia and 1 of secondary anemia referable to nephritis in which cholesterin was used for therapeutic purposes, the aim being to counteract any hemoly- sins that might be active in a manner analogous to the action of cholesterm on cobra lecithide. Of the 3 cases, one patient remained unimproved, while in the other two cholesterin was decidedly beneficial. The latter case was in a wretched condition, with intense dyspnea, ascites, pleural effusion, edema, and a red count of 750,000 with 18 per cent, of hemo- globin. After a week the count had risen to 1,750,000 and the hemoglobin to 30 per cent., while the threatening symptoms had all disappeared. The improvement was thus quite remark- able, but after a few weeks no further gain was obtained and still later a re- lapse occurred which ended fatally. Reicher (Bed. klin. Woch., Nu. 41-42, 1908). When cases prove refractory to ar- senic the writer found cholesterin efficient in daily doses of 1 to 2 Gm. (15 to 30 grains) administered in cachets or oily solution. M. Roch (N. Y. Med. Jour., Mar. 8, 1913). Glycerin has also been tried in para- sitic pernicious anemia, as a result of Tallqvist and Faust's suggestion that glycerin might combine with the lipoid substance assumed to be responsible 626 ANEMIA, SECONDARY (DA COSTA AND JUMP). for the disintegration of the red cor- puscles and thus combine to form a harmless product. The special lipoid substance found in the anemia from intestinal parasites proved to be oleic acid, and this combines with glycerin to form triolein. In the first of 2 cases in which glycerin was tried, the result was very encouraging, and in the second administration of 3 tablespoonfuls of glycerin a day, with lemon juice, was followed in the course of two and a half months by an increase in the red corpuscles from 990,000 to 4,760,000, and of hemoglobin from 20 to 90 per cent. No other drugs were given except a little antipyrin and cafTein for a day or so to combat a neuralgic headache. Vetlesen (Norsk Mag. f. Laeger, Oct., 1909). Operative treatment of pernicious anemia was introduced by Eppinger, of Vienna, splenectomy having first been performed by this surgeon in 1913 on the sound plea that the red cells were chiefly destroyed in the spleen. As Thayer states, however, it seems a serious matter to expose the patient to the extra danger of so severe an operation, when, as is well known, some patients may live years without operati\e intervention. The mortality of splenectomy ap- pears to be about 11 per cent. The best results of splenectomy are said to be obtained in the treatment of hemolytic jaundice. Eliot and Kava- nel in 48 cases collected in 1915 re- ported only 2 deaths, a mortality of 4.2 per cent. Krumbhaar in 1916 had collected 156 cases of pernicious ane- mia treated by splenectomy with 30 deaths. The Mayo Clinic reported 32 splenectomies for pernicious ane- mia up to April 1, 1916, with 3 deaths, or 9.7 per cent, mortality. Of the survivors, 22 or 78 per cent., showed continued improvement; of 16 fol- lowed up for 6 months, 11 continued to improve and 3 had relapses. From the experience of the Mayo Clinic it would seem that splenectomy should be considered where the patient is youthful and middle aged, where he shows good general resistance, where splenic enlargement is of moderate degree, and where there is evidence of hemolytic action. The treatment of pernicious anemia by splenectomy is still on trial and is apparently merely palliative. There is, however, reasonable hope for im- proved results. J. B. Deaver (Phila. Co. Med. Soc; N. Y. Med. Jour., July 27, 1918). Among 50 cases of pernicious ane- mia treated by splenectomy more than 3 years before, the writers found that 10 patients (21.3 per cent.) of those who had recovered from the operation survived splenectomy 3 years or longer. Five patients (10.6 per cent.) had survived more than 4% years. In addition to the imme- diate remission which occurred con- stantly following splenectomy, splen- ectomy prolonged life in at least 20 per cent, of the cases. The patient shows a more marked immediate im- provement in the type of case in which there is evidence of active hemolysis. Splenectomy may be rec- ommended in pernicious anemia when, in view of all the circumstances, per- sonal as well as medical, the possi- bility of prolongation of life appeals to the family and patient. Occasion- all}' it may be performed to bring about an immediate remission. Gif- fin and Szlapka (Jour. Amer. Med. Assoc, Jan. 29, 1921). Frederick P. Henry AND J. Norman Henry, Philadelphia. ANEMIA, SECONDARY, OR SYMPTOMATIC. — DEFINI- TION. — A deficiency either in the quantity or the quality of the blood, affecting the blood mass or the cellular and albuminous constituents. Genuine secondary anemia is essentially a symp- ANEMIA, SECONDARY (DA COSTA AND JUMP). 627 tomatic disorder, referable to obvious pathological conditions, which deplete the blood volume, diminish the number of erythrocytes, and reduce the amount of hemoglobin and albumin. When summed up all cases of ane- mia include very few of the so-called primary anemias and a great man}' forms of secondary anemia. The secondary or simple anemias, anal- yzed from the standpoint of cause, might be grouped under: 1, infec- tions; 2, those following hemorrhage, manifest or concealed; 3, those due to some form of intoxication, in these days new poisons are being en- countered, and cases, such as had been termed pernicious anemia, might be due to TXT poisoning; 4, para- sitic anemia;, 5, anemias that were expressive of some deep seated, per- haps overlooked, neoplasm. Alfred Stengel (Trans. Phila. Co. Med. Soc; X. Y. Med. Jour., July 27, 1918). TYPES OF SECONDARY ANEMIA. — It is convenient to classify the simple secondary anemias into several clinical groups which relate directly to the predominant factor active in the individual case. While a classification of this sort must needs be imperfect, for fre- quently several factors are concerned in a single instance, it will serve to designate the important underlying condition of which the blood im- poverishment is symptomatic. The following groups are sufficient for the inclusion of all anemias of secondary origin. I, posthemorrhagic ; II, infec- tious and toxic, and III, trophic. I. Posthemorrhagic anemias com- prise that varied class of cases directly traceable to bleeding, irrespective of its extent, duration, and character. In this group, therefore, are included the acute anemias due to loss of blood by trauma, operation, abortion, par- turition, epistaxis, hemoptysis, gastric and intestinal ulcer and neoplasm, hemorrhagic pancreatitis, and under the same heading are the grave ane- mias consecutive to the rupture of an aneurism, of a Fallopian tube, and of a large mass of varicose veins. The hemorrhagic diseases (purpura, hemophilia, scurvy), hemorrhoids, and uterine fibroids, all of which are cap- able of causing persistent, though per- haps moderate, loss of blood, may also excite a secondary anemia, perhaps of pronounced severity. Various authors have described certain differences which they deemed to be fundamental, but the experi- ments of the writer indicate that al- though there are ininor differences, all the essential features of anemia produced by toxins can be produced by hemorrhage. Milne (Jour, Exper. Med., Sept., 1912). In a comprehensive study of blood transfusion in the treatment of severe posthemorrhagic anemia and the hemorrhagic diseases, the writer found that in acute and chronic post- hemorrhagic anemia, no other rem- edy would compare in efficiency with whole blood in producing hemato- poietic stimulation. In the acute variety (following trauma, labor, op- eration, or accidental cause, or as complication of ectopic pregnancy, gastric or duodenal ulcer, typhoid fever, etc.) a single large transfusion is indicated, while in the chronic type (that resulting from repeated small losses of blood) better results are ob- tained by giving serial transfusions of small or moderate amounts of blood. E. W. Peterson (Med. Rec, Apr. 15, 1916). II. Infectious and toxic anemias develop chiefly as the result of hemo- lytic agencies, and are encountered in the specific infections, malignant dis- ease, intestinal helminthiasis; in poi- soning by certain so-called blood 628 ANEMIA, SECONDARY (DA COSTA AND JUMP). poisons — nitrobenzol, potassium chlo- rate, lead, mercury, arsenic, antimony ; and in states of autointoxication — uremia, cholemia, pregnancy. Of the acute febrile infections that account for anemia of moderate intensity, enteric fever, sepsis, variola, erysipe- las, rheumatic fever, and scarlatina may be named as typical examples. The anemia excited by malignant neoplasms is attributable partly to the action of circulating tumor-toxins and partly to concomitant factors, such as hemorrhage, ulceration, and interference with nutrition, as in esophageal and gastric growths. The anemia of helminthiasis is due prin- cipally to the hemolytic action of poisonous substances elaborated by the worm, notably in the case of uncinariasis and bothriocephalus dis- ease, and to a less extent in persons harboring oxyurides, ascarides. and tilarise. Helminthiasis anemia is also favored by the associated gastroin- testinal disorders, and. in uncinari- asis, the parasites suck blood from the intestinal vessels of the host and pour out an absorbable anticoagulant material which may act deleteriously upon the circulating blood-cells. The luetic virus materially damages the hemoglobin and erythrocytes, and syphilitics as a class are subject to a form of toxic anemia which as a rule attains its greatest development dur- ing the tertiary stage of the infection. In malarial fever it is probable that the presence of a circulating specific malarial toxin, produced by myriads of parasites, has much to do with provoking the attendant anemia, and it is certain that in this infection the blood must suffer from the whole- sale destruction of parasitiferous erythrocytes. Report of experiments showing that vitiated air can cause anemia in human beings only when there is some predisposition of a toxic order to influence the blood-making organs. The bad air of prisons, workshops, etc., causes only pseudoanemia, i.e., pallor of the integument, but no changes in the blood. Krotkofif (Roussky Vratch, Jan. 18, 1914). Aplastic anemia in young persons is the result of the exhaustion of function of a bone marrow congeni- tally defective in power of endurance, in older persons it is the result of some poison or poisons which, acting on the bone marrow, destroys its function and leads to death. A pathologic hemoly- sis as an essential part of this syndrome has not been shown. Rennie (Med. Jour, of Australia, June 14, 1919). In a case reported by the writer, exposure to the X-rays for about 15 j^ears was considered to be the cause of the anemia. It was of short dura- tion, the patient succumbing in about 6 months, and sjmiptoms were com- plained of only during the last 2 months. The rapid diminution in the red and white corpuscles was very noticeable, the reds disappearing at the rate of, roughly, 250,000 per week, and the whites sinking to 840. The color index was never over 0.9. The differential count was remarkable: Polynuclears, 41 per cent; lympho- cytes, large, 54 per cent. ; small, 4 per cent.; eosinophiles and baso- philes, none. Larkins (Lancet, Apr. 16, 1921). III. Trophic anemias, or those of nutritional origin, are met with com- monly in subjects that suffer from chronic malnutrition due to faults in the quantity and quality of their food, to defective absorption and assimilation, or to a combination of these two causes, and in many such instances deficient air and sunshine, lack of exercise, confining occupation, and unsanitary surroundings must likewise be reckoned with as contrib- ANEMIA, SECONDARY (DA COSTA AND JUMP). 629 uting; elements. Drains upon the albumins of the system, as in habit- ual nephritis, persistent suppuration, prolong-ed lactation, and chronic dys- entery, ultimately provoke well-de- fined, stubborn anemia of the trophic type. Von Jaksch's anemia belongs to the category of trophic anemias. In 1889 von Jaksch described a case of leucemia in a child of 14 months, and in the following year he reported 3 cases of enlarged spleen in children, a condition which he called anemia pseudoleucemica infantum. This was characterized by a diminution in the hemoglobin and in the number of red cells, marked persistent leucocytosis, sometimes glandular enlargement, slight enlargement of the liver, a marked en- largement of the spleen, which was out of all proportion to the size of the liver, and a tendency to recovery. The blood-pic- ture is characterized by a great diminu- tion in the red cells and the hemoglobin, and a persistent leucocytosis. Most of the patients show a definite tendency to re- cover. The abnormal blood-picture in those who lived might persist for a very long period of time. This form of ane- mia is frequently associated with rickets. The symptoms are those of anemia in general, pallor, edema, weakness, dyspnea, etc. a large liver, and a very large spleen, with a characteristic blood-picture. The onset is gradual and the patient is usu- ally brought in for treatment when a well marked enlargement of the spleen has developed. After tuberculosis, diphtheria and the eruptive diseases, Leishman's anemia or leishmaniosis is the most prevalent disease in southern Italy. Families living in rural districts or having much to do with domestic animals are specially subject to it. Direct contagion can be incriminated in most of the cases, the parasite probably being transmitted by means of bedbugs. There is also much to sustain the view that dogs and dog fleas are responsible for its transmis- sion. Franchini has recently found the parasites in gnats. G. Caronia (.Archiv f. Kinderheilk, Bd. Hx, Nu. S-6, 1913). Aplastic anemia develops as hemor- rhagic purpura which continues a steadily progressive course until the patient succumbs to the anemia in the course of a tew weeks or months. In the case of a woman of 33 the patient had contracted syphilis 14 years before but was apparently in perfect health when given an addi- tional mild course of mercury and salvarsan. Eight days after its con- clusion the hemorrhagic purpura de- veloped and progressed to a fatal termination in 15 days. In this, as in all the cases on record, the small numbers or total absence of blood- platelets was a striking feature of the case. E. Frank (Berl. klin. Woch., Sept. 13, 1915). School Children's. — The writer studied 42 cases of a form of anemia found in school children character- ized by eosinophilia. Various para- sites were always present in the feces. The degree of eosinophilia is uninfluenced by the kind of parasite present. He advises, therefore, that in all cases of anemia in school chil- dren the blood should be carefully examined for eosinophilia and the stools be searched for the ova of in- testinal worms. Scaroni (Gaz. degli Osped. e delle Clin., Jan. 7, 1917). PATHOLOGY.— The principal pathologic alterations incident to ane- mias of the secondary type relate to the composition of the circulating blood and to the histology of the bone-mar- row, of which the former changes are the more important, and, obviously, more readily available to the clinician. The blood changes vary within wide limits, depending upon the grade and the chronicity of the individual case; but in general it may be stated that they are of very moderate intensity in the average example of general symp- tomatic anemia. There is a more or less decided diminution in the number 630 ANEMIA, SECONDARY (DA COSTA AND JUMP). of erythrocytes (oligocythemia), with a stroma degeneration, whereby the tolerably proportionate reduction in tlie affected cells no longer react toward percentage of hemoglobin {oligochro- acid aniline dyes, as they do normally, meniia), and, in severe cases, one ob- but show a selective affinity for basic serves structural changes implicating colors, by which the stroma of the the erythrocytes' stroma and eventually healthy red corpuscle is never stained, leading to the production of corpuscular when exposed to a mixture contain- deformities of shape (poikilocytosis), ing both acid and basic dyes. The and of size (megalocytosis; micro- behavior of the leucocytes in second- cytosis). Not always, however, is the ary anemias is most inconstant. In hemoglobin-erythrocyte reduction pro- chronic cases, especially those due to portionate, for in some forms of sec- trophic defects, and in certain of the ondary anemia the hemoglobulin loss is slowly progressive toxic anemias the greatly disproportionate to that of the leucocyte count does not deviate cells, as, for example, in so-called from normal, or, if it shows any ap- "syphilitic chlorosis," which, hemat- preciable change, becomes subnormal ologically. counterfeits maiden's chlo- (leucopenia). In these leucopenic ane- rosis; on the contrary, in other types mias it is also the rule to find a dis- the erythrocytes suffer chiefly, as in proportionately high percentage of that variety of parasitic anemia pro- lymphocytes (relative lymphocytosis), voked by the Bothriocephalus latiis, these cells increasing in number chiefly whicli apes true pernicious anemia in at the expense of the polynuclear every detail of the blood-picture. forms. These facts call for great caution in The writer considers a high bili- attcmpting to diagnose a secondary ""ubin content of the blood serum as 1,1,111 1 " an instructive sign of abnormal anemia by the blood changes alone, , , • ^t., i i . i •^ f 1 1- hemolysis. that the spleen is the without due regard for the discovery „^^j,^ ^^^^ ^^ destruction of red cor- of some adequate causal factor to puscles has been confirmed anew by be correlated therewith. In active, his and Daniels' recent experimental severe cases of anemia young, nu- research with injections of hemolytic , , , ,, , . 1 ; i V serum into rabbits before and after cleated erythrocytes (normoblasts) es- , , n^ i .. . . a J ■> ^ splenectomy. the latter protected cape prematurely from the bone- the animals against the hemolysis to marrow and appear in the circulating a great extent. The hemoglobin re- blood in limited numbers, and in the leased from the corpuscles destroyed event of intense retrograde marrow »" ^'^^ ^P'^*^" '^ '^^''"^^ ^'°"S ^^^^ P^":" , -11.1 tal vein to the liver, where it is split changes an occasional nucleated cor- . ^ .... , . j ^ u ° up into bilirubm. L. S. liannema puscle of fetal type (megaloblast) also (Nederlandsch Tijdsch. v. Genees- may be observed. With such evidences kunde, Nov. 3, 1917). of high-grade blood deterioration one Other anemic blood changes, of also meets with cells disfigured by very minor importance, comprise in- atypical staining proclivities (polychro- creased rapidity of clotting and sub- matophilia), and with cells whose proto- normal specific gravity values, plasm is stippled with fine and coarse Anemia appearing in the face of basic granules (granular basophilia), active hemorrhage, of acute infectious both of which abnormal findings processes, and of malignant disease is point to a considerable degree of ordinarily attended by a leucocyte ANEMIA, SECONDARY (DA COSTA AND JUMP). 631 increase affecting mainly the poly- nuclear cells {polynudear ncutrophilc lencocytosis), and in helniinthetic dis- eases of recent origin there is a very constant increase in the percentage of eosinophile cells (polynuclear eosino- phile ieucocytosis). The presence of small numbers of immature polynuclear neutrophile cells (myelocytes) in the blood is frequently noted in many of the severer anemias of symptomatic character, irrespective of the presence or absence of a Ieucocytosis. The bone-marrow in a severe case of anemia undergoes a moderate de- gree of softening and acquires a some- what reddish hue, the attendant his- tological changes of this transforma- tion consisting of a hyperplasia of the lymphoid elements and a diminution in the number of fat-cells, which are replaced by marrow-cells or myelo- cytes charged with neutrophilic and eosinophilic granulations. Nucleated erythrocytes or erythroblasts, chietiy of the normoblastic type, are numer- ous when active powers of hemo- genesis persist. H. C. Bunting's studies of the blood and bone-marrow in rabbits rendered anemic by the injection of hemolytic poisons has thrown a clear light upon the dif- ference betv\'een the marrow changes incident to anemias of different grades of development. This investi- gator showed that hemolytic anemia excited by saponin is associated with more or less effectual depletion of the marrow-centers wherein prolifera- tion of the blood-cells takes place, and with fragmentation and other degenerative changes in the other marrow-cells, the blood-picture be- traying this grave myeloid lesion virtually corresponding to that of true pernicious anemia in man. In contrast to these fmdings, posthemor- rhagic anemia, despite the presence of characteristic changes in the pe- ripheral blood, does not affect the in- tegrity of erythrogenic and leucogenic centers of the marrow. Furthermore, it would appear that in some in- stances the proliferating centers of the marrow become quite replaced by scar tissue, in which event the hematopoietic function, now impos- sible for the crippled marrow to CKTvy on, is undertaken by the spleen. The visceral changes to be noted in cases of chronic secondary anemia in- clude granular degeneration of the liver, kidney, and heart, and, in some instances, fatty changes in these organs. These lesions depend more upon concomitant disturbances, such as toxemia and nutritional faults, than upon the effect of the anemia per se, and it seems within the bounds of reason to assume that they arise in part from an undue visceral activ- ity excited by the organism's attempt to maintain a normal process of oxidation. The liver, the spleen, and fre- quently the lymph-nodes assume a fetal type in grave or pernicious ane- mias as far as their cellular charac- ter is concerned. Erythroblastic cells and newly formed leucocytes appear in them, while the blood-making or- gan of the adult, the bone-marrow, shows likewise a picture of greatly increased activity. The writer, to- gether with Heinecke, has interpreted these phenomena as reparative in nature in opposition to another con- ception of the findings which seeks to interpret them as the primary re- sult of some unknown harmful agent. Von Domarus has greatly strength- ened the standpoint maintained by the writer by producing experimental anemias in animals and showing that the changes in the blood-making or- 632 ANEMIA, SECONDARY (DA COSTA AND JUMP). gans of intrauterine as well as of - extrauterine life were similar in these animals to those observed in patients with pernicious anemia. Meyer (Miinch. nied. Woch., June 2, 1908). SYMPTOMATOLOGY. — Pallor, the suggestive liallniark of all ane- mias, is usually well marked in the secondary type of this affection, and the subject's skin, mucosa, and nails may become so l)lanched as to ap- pear almost colorless. In other in- stances, the loss of color is much more moderate, and in still others the actual pallor is more or less ob- scured by a yellowish or muddy or icteroid staining of the integument. Tn passing, it may be remarked that pallor of itself does not justify a diagnosis of anemia, for many persons with unnaturally pale faces have a perfectly normal blood-picture, in view of which the blood examination must invariably be the court of final appeal. Aside from pallor, the most con- spicuous symptom groups in anemia are attributable to disturbances of the cardiovascular, the gastrointesti- nal, and the nervous systems. Of the circulatory symptoms, dyspnea, car- diac palpitation, and dropsical swell- ing of the ankles and legs are likely to prove sources of great distress to the patient, while the discovery of hemic murmurs at the base of the heart and of a venous hum at the root of tlie neck affords findings of the utmost pertinence. These anemic murmurs, generally situated at or near the pulmonic orifice, are almost invariably systolic in time and re- stricted to the precordial area or to its immediate vicinity. They are soinetimes associated with a percepti- ble increase in the size of the cardiac outline, indicative of dilatation of the heart from defective myocardial nu- trition, overstrain, and, exceptionally, fatty degeneration. The distinct positive venous pulse observed in endocarditis is not an un- common symptom of anemia and is due to a relative muscular insuffi- ciency of the tricuspid orifice. The cause is the same as that of the mitral insufficiency so common in chlorosis. In order to make sure of the functional character of the con- dition it is important to bear in mind that a relative tricuspid insufficiency in anemia develops at the same time as the mitral insufficiency, while in endocarditis the tricuspid lesion usu- ally develops long after the mitral. Besides, disturbances of compensa- tion are usually absent. Von Leube (Zeit. f. klin. Med., Bd. Ivii, Nu. 3-4. 1905). The foregoing symptoms, which are prominent only in severe anemias, promptly vanish as the normal compo- sition of the blood is regained, and frequently in such cases the pulse is inordinately rapid, of low tension, and subject to arrhythmic disturbances, while occasionally the abrupt, jerky beat of the Corrigan pulse is super- ficially imitated. Murmurs are audible inside the skull in anemia from any cause and grow less and less audible as the blood- supply returns to normal. In about 50 patients the murmurs were often distinct in hemorrhagic gastric ulcer or cancer, in pernicious anemia and with lesions localized in the skull. They were more pronounced with abnormally low hemoglobin content than with low corpuscle count. H. Koster (Zentralbl. f. innere Med., Nov. 15, 1913). Of the symptoms referable to the gastrointestinal tract, anorexia, pyrosis, abdominal distention, sensitiveness, and unrest, nausea, and constipation may ANEMIA, SECONDARY (DA COSTA AND JUMP). 633 attract attention. In the average case of secondary anemia the motor powers of the stomach are unaltered, and the secretion of hydrochloric acid remains normal or is even increased. On the other hand, there is a decided tendency toward weakening the intestinal motor function, although the juices of the gut flow naturally (Boas, v. Noorden). Ulcers in the throat may be due to anemia or lowered vitality. The writer has seen 3 cases; all in young women. The ulcer is round, small, with scanty secretion. There was no history of either tuberculosis or syphilis and no swelling of the glands. Pohly (N. Y. Med. Jour,, Aug. 27, 1910). The anemic vomiting in anemic girls is apt to be mistaken for gas- tric ulcer. The symptoms are pain in the epigastrium and vomiting ex- cited by almost everything that is placed in the stomach. Its mucous membrane is so hyperesthetic that whatever touches it causes pain and vomiting. This is often associated with pain and tenderness of the skin and muscles under the left breast, though there is nothing the matter with these structures. Whereas in ulcer solid food gives more pain than liquid, in anemic vomiting the pain and vomiting have not a constant re- lation to meals; they may have some of their worst attacks apart from food altogether. Sudden exertion, or being tired out, will bring on the same pain. Beddard (Pract., Mar., 1912). Of the various nervous disturbances, headache, vertigo, syncope, insomnia, phosphenes, muscae volitantes, and tin- nitus aurium are familiar examples. Moderate, irregular fever is occasion- ally observed as a consequence of nerv- ous factors and as a sign of septic processes. Most anemics, particularly those of chronic character, complain of unnatural fatigue, both mental and muscular, and in severe cases the pa- tient may be incapable of sustained in- tellectual effort, exhibits curious mental caprices and irritability, and develops a myasthenia amounting almost to com- plete debility. Six cases of anemia of the central nervous system resulting in sclerosis of the cord. The onset of the disease is gradual. The symptoms are very variable as are the changes in the spinal cord. Sometimes the poste- rior columns are involved; sometimes the lateral tracts are added; again, there is a diffuse sclerosis of the en- tire cord. Paresthesia and ataxia may persist for j^ears with few changes in the cord, or the intensity of the alterations may be much greater than the clinical symptoms. The mental state may be dull and inattentive, and there may be various muscular palsies of eye muscles or face. Leopold (Med. Rec, Mar. 5, 1910). The blood-picture of secondary anemia is in no wise distinctive, as already pointed out in the remarks on the pathology of this affection. Usuallv there is a moderate and roughly parallel loss of hemoglobin and erv'throcytes, the former being (diminished approximately 45 per cent, and the latter 30 per cent, below the normal standard, in the case of average severity. The stained film generally shows nothing more than simple pallor of the erythrocytes with, perhaps, a few misshapen cells and some tendency tow-ard irregu- larity in their diameter measure- ments. Normoblasts and erythroc3'tes with stroma degeneration are met with only in anemias of great inten- sity, characterized by excessive de- struction of the cells, and under such conditions an occasional megaloblast, indicating a fetal reversion of the marrow, mav enter the blood-stream. 634 ANEMIA, SECONDARY (DA COSTA AND JUMP). Leucocytosis, developing; under the circumstances referred to in a pre- ceding paragraph, means stimulation of tlie marrow's functional activity, the exhibition of which is regulated largely by the nature of the excit- ing cause and by the individual pe- culiarities dominant in the case under consideration. The coagulation-time {hcmatopexis) of the blood is short- ened in close relation with the degree of existing anemia. The blood lipoid values in anemia were found by the writers to be nor- mal, or nearly so, as long as the per- centage of blood corpuscles remained above half the normal value. When the percentage was below this level al)normalitics appeared which, in the order of their magnitude and also of the frequency of their occurrence were (1) high fat in the plasma, (2) low cholesterol in the plasma and oc- casionally in the corpuscles, and (3) low lecithin in the plasma. The lipoid composition of the corpuscles was found to be normal in prac- tically every case. Bloor and Mac- Pherson (Jour. Biol. Chemistry, July, 1917). DIAGNOSIS.— The diagnosis of secondary anemia invariably must be based upon a suggestive blood picture plus the discovery of some factor responsible therefor. Given a blood jioor in hemoglobin and erythrocytes in an individual suffering, for instance, with sepsis or gastric cancer or rheu- matic fever, the diagnosis can tax no one's intelligence. But given an ob- scure etiologic factor in an anemic person, one must carefully interrogate through a long list of potential causes of blood impoverishment in order to detect a satisfactory cause. The dif- ferential diagnosis of secondary ane- mia includes the consideration of pseudoanemia, chlorosis, pernicious anemia, splenic anemia, leukemia, chloroma, and liodgkin's disease. Pseudoanemia versus true anemia is a differentiation constantly to be borne in mind in examining a patient for the first time. Spurious anemia, which, of course, shows a normal blood report, is characterized by un- natural pallor of the skin and mucous surfaces, probably of hereditary origin and explainable on the grounds of a deficiency of skin pigment and abnor- mal constriction of the superficial capillary network. Apart from pallor, the affection is quite symptomless. In this connection may be mentioned an angiospastic type of pseudoanemia, recognized by the abrupt appearance of attacks of transient grayish pallor induced by emotion, fatigue, exposure to cold, and similar vasomotor stimuli. Chlorosis, though its blood picture may be precisely counterfeited by certain forms of secondary anemia (such as Chlorosis, q.v.), is readily dis- tinguished from the latter by its oc- currence exclusively in girls and in young women who exhibit, with pass- able fidelity, a varied train of un- mistakable chlorotic stigmata — green- ish pallor, menstrual disturbances, perverted appetite, indigestion, con- stipation, slight enlargement of the thyroid gland, and many symptoms referable to functional neuroses. Pernicious anemia in its typical form gives rise to three m.ost pertinent blood changes : extreme oligocythe- mia combined with a disproportion- ately slighter oligochromemia ; the presence of numerous erythroblasts, of which cells those of a megaloblastic type predominate ; and many de- formed and otherwise degenerate er\'throcytes, notably megalocytes and basophilic corpuscles. The first ANEMIA, SECONDARY (DA COSTA AND JUMP). 635 detail of this blood-picture means nomena, and, arising from no apparent that the hemoglobin content of the cause, pursues a fatal course of short erythrocytes (color index) is unnat- duration, unbroken by periods of urally high ; the second indicates remission. active compensatory hemogenesis and Splenic anemia, a rare and somewhat fetal reversion of the bone-marrow, questionable clinical entity, causes a and the last points to the manufac- blood deterioration in no wise different ture by the marrow of numerous from that accompanying an ordinary faultily formed, functionless erythro- symptomatic anemia with leucopenia. cytes, of little or no use as oxygen But in splenic anemia there is an idio- carriers. Leucopenia, relative lym- pathic splenomegaly without enlarge- phocytosis, and a moderate degree of ment of the lymphatic glands, and, in myelocytosis are among the other the later stages of the disease, biliary hematological features of this disease, hepatic cirrhosis, jaundice, and ascites In addition to these findings, it must supervene, to complete the symptom be recalled that true pernicious ane- group sometimes spoken of as Banti's mia arises insidiously, is entirely un- disease. Disturbances due to severe connected with any tangible causal anemia and to the pressure of an enor- factor, and invariably progresses mous spleen are generally conspicuous, steadily, perhaps with temporary and the disease is likely to develop periods of remission, to a fatal ter- insidiously, drags along for several mination. An aplastic type of per- years from bad to worse, and eventually nicious anemia has been described, in kills. which, owing to extraordinary atro- Leukemia is easily distinguished from phy of the bone-marrow, there arises secondary anemia by means of its dis- an intense oligocythemia and oligo- tinctive blood picture, as well as by chromemia with but trifling evidence certain objective symptoms. In the of structural degeneration and nuclea- myelogenous form the combination of tion of the red corpuscles. In at- a high leucocyte count and excessive tempting the antemortem differentia- numbers of myelocytes (myelemia) is tion of aplastic anemia and anemia of conclusive, and in such cases the spleen the symptomatic variety (which at- is generally enormous ; in the lymphatic tempt must needs frequently be con- variety the detection of a high absolute jectural), attention should be paid and relative lymphocytosis (lymphcmia) especially to these hematological pe- is equally convincing, and here it is the culiarities of the first-named disease : rule to find great hyperplasia of the relatively low color index ; absence lymphatic glands. of erythroblasts of both types — Chloroma may account for an anemia normoblasts and megaloblasts ; scar- identical with that of the secondary city of cells showing stroma defects type, and it may also produce a blood and anomalies of shape and size, and picture closely comparable to that of extreme lymphocytic leucopenia. It lymphatic leukemia. In the former is also helpful to remeinber that instance the low hemoglobin and eryth- aplastic anemia is prone to affect rocyte values are accompanied by a young women, is commonly asso- relative increase in the number of ciated with severe hemorrhagic phe- lymphocytes, though the total leucocyte 636 ANEMIA, SECONDARY (DA COSTA AND JUMP). count does not exceed normal, while in the latter the blood shows great anemia with decided lymphemia. This being the case, one must recognize chloroma not by any distinctive blood formula, but by the chloromatous symptom-complex, made up of exoph- thalmos, deafness, severe orbital pain, elastic swellings in the orbital and tem- poral regions, and the formation of metastatic "green tumors" in the peri- osteal structures. In Hodgkin's disease, which in time gives rise to high-grade secondary anemia, the existence of a progressive glandular hyperplasia in the neck, axilla, and groin is conclusive evidence, apart from the presence of pressure symptoms, irregular fever, cutaneous bronzing, asthenia, and extraordinary emaciation, which together spell this malignant affection. PROGNOSIS.— It is scarcely nec- essary to state that the prognosis in a given case of secondary anemia must depend upon the circumstances prevail- ing in the instance in question, the character, duration, antl curability of the primary lesion being the decisive determining points of the forecast. The outlook in gastric cancer, for ex- ample, is very different from that in simple inanition or in one of the milder infectious diseases. On the whole, secondary anemia is a symptom that is promptly amenable to intelligent treat- ment, in strong contrast to which fact is the utter hopelessness of accomplish- ing a permanent cure in those deadly primary diseases of the blood, perni- cious anemia and the leukemias. TREATMENT.— Iron and arsenic, nutritious food, and correct hygiene will cure secondary anemia — provided that the essential cause of this symptom be removed. It is just as important to attend to a mass of bleeding piles or to treat an albuminuria in an anemic per- son as it is to prescribe hematinics, and, by the same token, it is equally impor- tant to outline a regimen in which an out-of-door life, ample sleep, and ra- tional personal hygiene are items of strict observance. The percentage of hemoglobin in in- fancj' is l)elo\v 55 at birth anil not rising above 70 during the period properly so-called of infancy. The number of red corpuscles varies between 5,500,000 and 6,0(X),000. This low hemoglobin per- centage is presumably due to an insuffi- cient supply of iron in its food and the lack of sufficient reserve of iron in the liver at birth. It is probable that true chlorosis never occurs in infants as a disease, but it is a fact that the chlorotic type of blood is very common at this age. Iron is, therefore, specially indi- cated, but it is difficult to get infants to take iron by the mouth, and it is very liable, moreover, to disturb the diges- tion. It is desirable, therefore, to give it some other way, and infants take it subcutaneously without injury. A very serviceable form for subcutaneous use is the aqueous soluJon of the citrate. This can be put up in pearls, each one containing a single dose, in which form it remains sterile indefinitely. It is ab- solutely non-irritating, and never causes abscess or induration if properly given, though it is somewhat painful. A glass syringe with an asbestos packing, which can be sterilized, and platinum needle that will not corrode with the iron. The average dose during infancy is three- quarters of a grain every other day. He has used this treatment in a number of cases in different types of anemia and with pretty satisfactory results, even in the severe cases. In the mild cases the improvement was very rapid, and the writer's experience leads him to recom- mend the use of iron in this way. The results are more marked and more quickly obtained than by oral adminis- tration, and it is much less liable to dis- turb digestion. It is especially indicated in severe cases of secondary anemia ANEMIA, SECONDARY (DA COSTA AND JUMP). 637 with digestive disorder and in those of a sclerotic type. J. L. Morse (Jour. Amer. Med. Assoc, July, 1910). A chlorotic type of anemia is ob- served in infants, in which there are pallor, digestive, circulatory, and nervous symptoms and a marked loss of hemoglobin, with a normal num- ber of red cells. The internal organs are normal; there are anemic mur- murs in the heart and vessels of the neck. The child is apathetic, quiet, has enlarged glands and sleeps poorlj'. This condition results when only milk is used, or when it is continued too long. The treatment is improved diet, and iron is ad- ministered in large doses. M. de Biehler (Arch, de Med. des Enf., Mar., 1913). A study of the action of iron in anemia led the writer to conclude that iron in proper doses elicits in a few days a stormy reaction in the bone marrow, which throws quanti- ties of young elements into the blood. In 10 cases of anemia with gastric ulcer, no benefit was evident under iron until large doses were given, and then the hemoglobin ran up rapidly from Zl to 82 and then to 100 per cent, and the reds to 5,024,000. Nageli (Schweizer. med. Woch., July 29, 1920). The form of iron to be administered, it is almost needless to state, should be readily absorbable, and unlikely either to upset digestion or to constipate. The carbonate of iron, in the pill suggested by Blaud, meets these requirements as well as any other preparation, and has the prestige of a long and dependable clinical usage. Excessive dosage is to be avoided, since the use of 6 or 8 grains a day will accomplish just as satisfactory results as a much larger amount, and will not tend to disturb the stomach or to constipate. Ferratin is a meritorious chalybeate, and is, if any- thing, even less astringent than Blaud's pill. Of the other iron preparations sometimes chosen for the same reason, the phosphate, lactate, and citrate all enjoy considerable vogue. The headache of anemia is due chiefly to the deficiency of hemo- globin, and consequent tendency to edema, with the simultaneous starv- ing of the meninges. It is usually frontal, but may be vertical. In cer- tain individuals of lymphatic type, subject to anemia, chilblains, and cold extremities, there may be a de- ficiency of calcium salts in the blood, and the administration of the calcium salts may be of great service in re- lieving the headaches of such pa- tients. The lactate should be given in doses of IS to 20 grains, three times a day. The headaches of the morning after copious libations have been ascribed to a lack of calcium salts in the blood, these having been precipitated by the organic acids con- tained in the wine. This headache may be very quickly removed by a dose of 20 to 30 grains of calcium lactate shaken up with a little water. Wilfrid Harris (Prac- titioner, July, 1906). There has been distinct progress in the treatment of anemia. The first of these is the method of direct trans- fusion introduced by Crile, whose ex- periments and results the author con- siders a brilliant illustration of the value of vivisection to humanity. The second is the use of colonic irriga- tions in pernicious anemia, as recom- mended by Herter, and successfully employed by Dittmar and Hollis. Herter's discovery that special putre- factive processes in the intestines are due to the prevalence of anaerobic bacteria, particularly the Bacillus capsulatus acrogenes, and the paral- lelism of their presence with the sj-mptoms of the disease suggested this treatinent by injections, which the writer considers a valuable thera- peutic advance. The third point touched on in his paper is the estab- lishment of the 'r'inical value of in- organic iron in the treatment of ane- 638 ANEMIA, SECONDARY (DA COSTA AND JUMP). mia. Ingested iron, like the carbo- hydrates, is converted into inter- mediate organic compounds and en- ters into the reserve iron stored up in the body, which is normally in excess of the needs of the system. S. J. Meltzer (Jour. Amer. Med. Assoc, Aug. 24, 1907). Employing the hemoglobin con- tents as an index of the degree of secondary anemia, as well as an actual erythrocyte count, the writers found that the hypodermic use of the citrate of iron in the secondary ane- mia of tuberculosis permitted them to control the anemia with almost mathematical precision, and that it actually in no single instance failed to improve the quality of the blood to at least some degree in the 256 cases in which they had employed it. Over 70 per cent, of these cases were in the advanced and far advanced classes, in wliich the anemia is a commonly manifested phenomenon. The measure was uniformly success- ful in raising the hemoglobin stand- ard to normal in all cases in which the patient might be considered to be doing well, or in which the status quo was seemingly maintained. It is not necessary to use a larger dose of citrate of iron than 0.05 Gni. Others who have used larger doses have ol)Scrved sudden vomiting to follow its administration. The tech- nique of the method is to employ the ordinary hypodermic syringe and needle, selecting the buttock as the least inconvenient site of injection, and giving an injection daily until the result is obtained. E. S. Bullock and L. S. Peters (Jour. Amer. Med. Assoc, Oct. 28, 1911). The writer employed numerous proportions of iron for many years, but in the majority of cases, the re- sults obtained were less favorable than those given by tlie use of other remedies. Foods rich in iron, that is available through digestion, are pref- erable. Whenever the cause of the anemia present can be ascertained the treatment is governed by such data. In those cases not the result of advancing cardiac, renal, hepatic disease, or carcinoma, excellent re- sults follow the use of readily digested foods, meat juices; and special attention to the gastric intes- tinal tract. The administration of red bone marrow showed in 60 cases of anemia that the red blood cor- puscles, and the hemoglobin were more rapidly increased by this method, together with the fact that the patients were always fed liberally of green fruit and vegetables, than by any other. Napoleon Boston (Buffalo Med. Jour., June, 1917). Arsenic is of indispensable value as an adjunct to iron in dealing with anemia, particularly those forms dis- tinguished by relatively excessive oligo- cythemia, as in those severe instances consequent to infectious and malignant processes. The time-honored Fowler's solution answers well in the majority of cases, but where an idiosyncrasy exists toward this preparation, as it frequently does, or where it is imperative to stimulate hemogenesis very rapidly, atoxyl (sodium anilarsenate) will prove the better form of arsenic. It should always be given hypodermically, in doses of from Yi grain to 2 grains, on alternate days, until the patient has received about 20 grains, after which the drug is discontinued for a week, and then readministered according to the plan originally followed. Given in this manner, one need not fear that lamentable complication, optic neuritis, which has been produced by the ill- advised use of atoxyl. Or arsacetin (sodium acetyl arsanilate) inay be used, in the same dose and by the same method advised for atoxyl, if it is thought best to employ an even less toxic preparation of arsenic, ^^'hile useful, manganese, phosphorus, red bone-marrow, hemoglobin, oxygen, and the cacodylates are in no sense adequate ANEMIA, SECONDARY (DA COSTA AND JUMP). 639 substitutes for iron and arsenic in the treatment of anemic conditions. Hypodermic medication with iron and arsenic, together with strychnine and the hypophosphites, offers a prompt and powerful reconstructive adjunct to the pure air, good food, and sen- sible hygiene that are essentials in pretuberculous conditions. The green ammoniated iron citrate can be mt re- duced into the system, without dan- ger, in doses of from 34 to US grains, while sodium arsenate is given in doses of from %o to %o grain. The injections of solutions of these drugs are given deeply into the muscles of the buttocks or back. Only slight pain attends the procedure, and a general feeling of well-being follows the treatment. A full dose of the iron wnthin five minutes causes a feeling of tension in the head, ting- ling sensations, and a flushing of the face. Doses larger than llS grains may cause nausea or vomiting. B. R. Shurly (Tour. Amer. Med. Assoc, June 16, 1907). Sufficient is known to justifj' more than a suspicion that William Hunter was correct in believing that perni- cious or infective anemia should be laid at the door of mouth infection. The writer's own experience tends to confirm this belief, particularly in 2 recent cases of pernicious anemia. In 1 patient rigid examination failed to reveal any focus of infection save the mouth, which showed a bad glos- sitis and pyorrheal abscesses about all the few remaining teeth. After the administration of 5200 c.c. (SV2 quarts) of blood by citrate trans- fusion at intervals, the use of salvar- san intravenously, the administration of hydrochloric acid and good food and rest, only very temporary im- provement resulted. When all of the infected teeth were removed, the patient made such rapid and marked improvement that he had now re- sumed a laborious occupation with the appearance of health and a blood exhibit approximating the normal. M. L. Graves (Trans. So. Med. Assoc; N. Y. Med. Jour., Jan. 12, 1918). The anemic subject should eat plentifully of nutritious, and, it must be insisted, palatable, food — red meats, strong- broths, eggs, butter, cream, fruits, and ferruginous vege- tables like spinach, asparagus, lentils, and cauliflower. If the appetite flags it may be advisable to whip it up with a glass of stout or of mild claret at mealtime, or by the use of the bitter tonics, the amount of food at the same time being intelligently re- stricted. Indigestion, if not fore- stalled by a rational dietary, must be cotnbated by such useful remedies as pepsin and hydrochloric acid, pan- creatin and diastase, pawpaw, char- coal, and bismuth. It is most neces- sary for the patient to have a free bowel movement each day, to insure which, if other measures fail, it is good practice to resort to cascara sagrada, phenolphthalein, singly or combined witli aloin, strychnine, and belladonna, and supplemented by a dram or two of Carlsbad salts dis- solved in a tumblerful of hot water, to be slowly sipped each morning di- rectly on arising. Intestinal fermen- tation, the bane of so many anemics, is best treated dietetically (eggs are notorious offenders), by intestinal irrigation, by tlie administration of cultures of the lactic acid bacillus, and by the use of B-naphthol, salol, bis- muth salicylate, phenol, and similar antifermentative drugs. In patients with troublesome nervous symptoms strontium bromide and the valerian- ates of iron, quinine, and zinc are helpful adjuncts to the therapeusis suggested above. In anemia due to autointoxication from the gastrointestinal tract, as 640 ANEMIA, SECONDARY (DA COSTA AND JUMP). often occurs in chlorosis: 1. Favor gastric functions by proper diet 2. Secure regular bowel movements by laxatives. 3. Begin the use of iron, giving following pill: Subcarbonate of iron, 0.10 Gm. (P/. grains) ; pow- dered aloes, 0.02 Gm. (% grain) ; extract of rhubarb, 0.05 Gm. (% grain); 2 pills before meals. Huchard and Fiessinger (Revue de therap., March 15, 1910). The writer advises the daily use of green vegetables, not only for the anemic and dyspeptic, but for the healthy as well. Chlorophyll has been given as such to the anemic, but doubtless cannot replace the fresh vegetables. Maillart (Corres.-Blatt f. Schweizer Aerzte, June 3, 1916). In a comprehensive study of the blood regeneration following simple anemia in the dog, the writers found that Blaud's pills are inert when added to various diets which do not favor rapid blood regeneration. In an ani- mal bled till the pigment was re- duced to a level of 40 per cent, below normal, followed by the institution of a meat diet, the pigment level nor- malized within 4 weeks. With milk diet the 40 per cent, level persisted. A fasting animal with access to water could reproduce the hemoglobin, showing that the body could reorgan- ize its elements into hemoglobin. Spinach was found to return the level of hemoglobin to normal and keep it there. Milk gave the minimum re- generation. Cooked liver and cooked beef heart produced the best regener- ation. Hooper, Robscheit and Whip- ple (Amer. Jour. Physiol., Sept. 1920). [It should be borne in mind that ex- periments in animals, particularly where the morbid process is produced artificially, do not alwaj's portray faithfully a blood disorder in man. — Ed.] In the management of actite ane- mias of grave character (i.e., post- hemorrhagic variety) the direct trans- fusion of an homologous blood, may prove to be a life-saving expedient. The technique and other details of this operation are discussed else- where in this work. (See Venesec- tion AND Transfusion.) In 8 instances of blood transfusion because of simple secondary anemia or because of anemia and malnutri- tion, the blood was usually obtained from the father or mother after phys- ical fitness was demonstrated by the absence of agglutination and hemo- lysis. The blood was withdrawn from a vein of the donor into a syr- inge and injected directly into the vein of the infant. The syringe was washed out with sterile salt solution before being refilled with blood. Satisfactory results were obtained in all but 1 case, although the children were all under two years of age, both in the digestive capacity and general health. C. G. Kerley (.'\mer. Jour, of Obstet., Lxxvi, 713, 1917). The writer advocates transfusion before operation in severe secondary anemias, on the basis of a case of uterine fibromyomata complicated by severe uterine hemorrhage of 6 weeks' duration. For 6 days following the patient's admission her general con- dition became much worse, the red blood count falling to 845,000 per cubic millimeter, when 600 c.c. of citrated blood were transfused into the median basilic vein. The eflfect was most decided. Three days later the temperature was normal, the vomiting had ceased, and control over the bladder and rectum had re- turned. The red cells had risen to 3,485,000, and the white cells had fal- len to 29,000 per cubic millimeter. Fifteen days later a subtotal hyster- ectomy was performed. This was followed by uninterrupted recoverj\ H. Williamson (Proc. Royal Soc. Med., London, xiii. Sect. Gynec. and Obstet., 149, 1920). Hydrotherapy and general mas- sage must be regarded as most useful aids to the drug treatment of anemia, and such measures, when sanely car- ried out, will do much to promote adequate excretion and secretion, to ANENCEPHALY. 641 maintain a healthy balance of the blood and lymph streams, and to stimulate oxygen and carbon dioxide interchange. A regimen of fresh air, sunshine, and gentle exercise is of great value, added to the fore- ofoine hvsfienic measures, and in this connection it is interesting to recall Gardinhhi's statement, recently voiced by Pope, that the presence of sunlight promotes the absorption of iron from the liver, where this metal, after inges- tion, is presumably stored in no in- considerable quantity. Very small doses of salvarsan — 0.05 or 0.075 Gm. (^ to V^ grain) — is a simple and harmless method of giving arsenic. It was extremely effectual in 50 cases, increasing the weight, improving the blood-picture •and subjective symptoms in all forms of secondary anemia and mild tuber- culosis. From 10 to 15 injections were given, the course being repeated after an interval of a few weeks. Kail (Miinch. med. Woch., July 7, 1914). The X-rays in large doses destroy the bone marrow, but ifi small doses enhance its activity. This explains their beneficial effects in severe ane- mia observed by the writers' with very mild exposures, the rays being filtered through 2 or 4 mm. of alumi- num. Vaquez and Aubertin (Arch, des mal. du Coeur, Sept., 1915). Case of von Jaksch's anemia in a child of 18 months on whom the writer performed a splenectomy, with good results. Red count, 2,700,000; hemoglobin, 45 per cent.; white cells, 12,000; polynuclears, 47 per cent.; normoblasts and megaloblasts were present. A spleen weighing 230 grams, showing a high grade meloid- ization, was removed May 11, 1915. Three weeks after the operation the red blood count had risen to 4,500,- 000, and the hemoglobin to 60. Pool (Annals of Surg., Ixiii, 122, 1916). In von Jakscli's aiiciiiia the most prominent feature of the symptom- complex is an enlarged spleen, but the other hematopoietic organs must be involved more or less extensively. The treatment has been unsatisfac- tory in the majority of cases; in 6 cases, however, treated bj- splenec- tomy the operation was followed by immediate clinical improvement. Frequently they tend to recover, when almost any treatment may be followed by improvement, while others progress to a fatal issue in spite of any treatment. R. G. Still- man (Amer. Jour. Med. Sci., Feb., 1917). J. C. D.\ Costa, Jr. AND Henry D. Jump, Philadelphia. ANENCEPHALY. -This mon- strosity is characterized by the absence in part or in toto of the brain and spinal cord. In most instances, however, the central nervous system is poorl}' de- veloped, and the child if borne alive is idiotic in proportion as the brain is de- ficiently developed. A curious and sug- gestive feature of this condition is that the adrenal cortex is poorly, if at all, de- veloped. Thus, Apert (La Presse Med., Oct. 28, 1911) states that this fact was first observed by Morgagni. It has been verified in hundreds of cases of anen- cephaly, pseudoencephaly, cyclopia and in a limited number of cases of hydrocephaly and microcephaly. In a case reported by F. B. Talbot (Med. Rec, Sept. 11, 1915) the child was blind, deaf, and apparently idiotic, and its metabolism was extremely low. An oper- ation for the possible relief of the blind- ness showed that the hemispheres were absent and replaced by cerebrospinal fluid. When the spinal cord is alone developed more or less, the movements are mainly reflex, as stated by Bronwer (Nederl. Tijdsch. voor Gyn., Aug. 16, 1913). He enumerates among the features to be as- certained the existence of syphilis, through the Wassermann test. Alfred Gordon (Med. Rec, Jan. 31, 1914) failed to obtain a positive reaction in the father of a case observed by him, but a history of alco- 1— il 642 ANESTHESIA. holism and of conception during a period- ical spree. The writer was able to diagnos- ticate a case of anencephaly before birth by means of X-ray. This in- dicates the value of radiography where Cesarean section is to be per- formed, this operation being rendered unnecessary where the presence of a monster is ascertained. J. T. Case (Surg., Gynec. and Obstet., Mar., 1917). S. ANESIN. See Chloretone. ANESTHESIA. —While the various anesthetics: Ether, chloroform, etc., are considered under their respective head- ings, many features of special interest can only be brought out by considering these agents collectively. Hence the present section. CHOICE OF ANESTHETICS.— A. S. McCormick (Summit Co. Med. Soc, Ak- ron, Ohio, Feb. 1. 1916) states that while the anesthetics most generally used are ether, nitrous o.xide, chloroform, ethyl chloride, their relative merits are as follows: Ethyl Chloride: The anesthetic and toxic stages are so close that it is too dangerous. Death rate, 1-2550 (1905-11). Its chief use is to begin anesthesia, for which it is quick and efficacious, but even then it is too dangerous. Chlorcform: Its many good points are outweighed by its one bad — that of being a dangerous heart depressant. Death rate, 1-2000. In warm climates it is safer, the rate being 1-8000. Nitrous Oxide: Alone it is a dangerous anesthetic. It has recently been exten- sively used, combined with oxygen. While safer than the original method, it is losing ground as too dangerous. The death rate, 1905-11, was 1-657. Crile states that in unskilled hands it is the most dangerous of all anesthetics. Ether: Admitted by all as safe, it is, beyond question, the safest and best of all anesthetics. Figures vary as to death, those of Wharton being 1-16,000 cases; Baldwin, 1-50,000; Rovsing (Denmark), 1-56,000; that is, death really caused by ether. At the Mayo Hospital ether was given 49,037 times in 13 years (1900-12) without causing death. Ether-oxygen is still safer and better. Less ether is required; the anesthesia is quiet and just deep enough; the oxygen counteracts the otherwise ether irritation; the patient's color is better than under any other anesthetic. Referring to experience in the late war, the writer notes that ether was used most extensively on account of its convenience and comparative safety. Scotch surgeons in the Brit- ish service clung to chloroform, how- ever, and their results were excellent. Ether-oxygen was a favorite method in serious cases, the oxygen from a low pressure tank being sent through a Shipway apparatus to provide a warmed ether vapor. When compact, portable American gas-oxygen de- vices became available, the nitrous oxide-oxygen technique won the favor of surgeons of all the allied armies. It gave promise of obviating to a great extent postoperative pneumonia. Warmed ether vapor was found quite superior to the drop method in every respect. Morphine was withheld from those in severe shock, as it lowered resistance in a marked degree; even ^ grain (0.016 Gm.) of morphine may invite disaster in the presence of shock or hemorrhage. Nitrous oxide- oxygen proved the anesthetic of choice in this condition. It was found very dangerous to alter the position of patients on the table after anes- thesia had continued for more than ''2 hour. Five c.c. (IV2 drams) of chlo- roform as a single dose proved to be an invaluable method for transient anesthesia or analgesia for minor procedures. Spinal anesthesia, used to some extent in base hospitals, was found to be especially dangerous in all patients showing a low hemoglobin index. W'. S. Sykes (Trans. Amer. Assoc, of Anesthet.; Jour. Amer. Med. Assoc, Aug. 9, 1919). Chloroform given by the closed method with rebreathing is, according to Gwath- mey, one of the safest of all anesthetics. It is agreeable, efficient, and easily stopped upon the appearance of danger signals. ANESTHESIA. 643 Late chloroform poisoning does not occur and complications are rare. Ether given by the vapor method is much safer, more agreeable, more effi- cient, is easily controllable, simpler to ad- minister, is not accompanied by loss of resistance against pus organisms, and not so frequently followed by complications as ether administered by the open drop method; the latter is unscientific. It has won unmerited favor within the past few years because of its apparent simplicity of administration and its supposed safety. It should be replaced b\' the simpler and safer vapor method. As a simple substitute for intratra- cheal anesthesia and the complicated apparatus required for it, the writer recommends vapor anesthesia with the Hitz bottle and foot-bellows, the latter being cheaper, more portable, and as efficient as an electric motor blower. The anesthetist soon learns to control the volume of air with the bellows, and the Hitz bottle is so made that any portion of the pumped air may be forced through the anes- thetic agent. A cylinder of oxygen is attached for emergency use or to augment the atmospheric air current from time to time if cjanosis is ob- served. Use of a chloroform-ether mixture is advocated. For induction the nitrous oxide-oxj^gen-ether se- quence is preferred. For young chil- dren, the essence of orange-ether se- quence is best, but for maintenance a mixture of chloroform and ether is advised. The proportion in most cases is, roughlj^ chloroform 1 part and ether 2 parts, but this is varied according to the type of patient, and the chloroform is increased in the mixture when difficulty in mainte- nance is anticipated. \V. H. Long (Amer. Jour. Surg., xxxiii, Anes. Supp., 11, 1919). Oil-ether colonic anesthesia should be used whenever the anesthetist is in the way, or whenever the element of fear dominates the patient. The obese alco- holic is the best subject for this special agent. Nitrous oxide gas should never be used alone, but always with oxygen. Prelimi- nary medication of some kind should be used in all surgical cases unless contra- indicated (Gwathmey). Minor surgical operations or those on the extremities are best done un- der nitrous oxide oxygen. For all operations requiring complete mus- cular relaxation, especially in abdom- inal surger)', the nitrous oxide ether sequence is the method of choice. Chloroform is too dangerous for general use, but it may more safely be used in combination with ether. Intratracheal insufflation is of value for thoracic operations. Rectal anes- thesia with ether in 5 per cent, oily solution is suited to operations on the head and neck combined with local anesthesia. Morphine and atro- pine injections are to be used sys- tematically. A. R. Egana (Semana Med., Apr. 29, 1920). Addition of a small amount of magnesium sulphate to the usual hypodermic of morphine greatly in- creases the value of the hypodermic. The author thus converts colonic an- esthesia into synergistic colonic anal- gesia, i.e., he obtains complete brain block hy using much smaller amounts of ether than heretofore and adding to it the effects of the combined morphine and magnesium sulphate. Furthermore, with 3 hjpodermic in- jections, each of % grain (0.008 Gni.) of morphine and 2 c.c. (^i> dram) of magnesium sulphate, supplemented by nitrous oxide and oxygen (the latter in high percentage) an analgesic state with unconsciousness and complete relaxation is secured which entirely eliminates the necessity for ether. Morphine, whenever indicated, may be given in a 25 per cent, sterilized solution of chemically pure mag- nesium sulphate. This increases the value of the morphine from 50 to 100 per cent. J. T. Gwathmej' (Jour. Amer. Med. Assoc, Ixxvi, 212, 1921). PRELIMINARY NARCOTICS.— Blumfeld (Proc. Roy. Soc. Med., viii, Sect. Anes., 15, 1915) held that the giving of narcotics preliminary to the anesthetic has great value in some cases, while in others it should not be used. As a routine 644 ANESTHESIA. measure these drugs should not be em- ployed with the single exception of atro- pine. He had never seen or heard of any ill-eflfects from it so used. Scopolamine and morphine seem risky drugs to pre- scribe indiscriminately. After the hypo- dermic the patient should be undisturbed and should not walk to the operating room. The main advantages of prelim- inary narcotics are: (1) a quiet induction; (2) less anesthetic used; (3) diminished after-effects. Atropine contributes to the first and second. Hewitt (Proc. Roy. Soc. Med., viii, Sect. Anes., 15, 1915) had found preliminary narcotics valuable when used with dis- criminating care. The anesthetist should be familiar with his patient's condition. Careful notes of 266 cases in which he had used morphine, atropine, and scopola- mine in different combinations show that atropine is a very valuable anesthetic, pre- venting undue secretion and causing little after-vomiting. It has no contraindications. Scopolamine is to be feared, Hoo grain (0.00065 Gm.) having caused in an elderly man profound narcotization. The injec- tions were made "A hour beforehand. Morphine is strongly contraindicated in certain cases: nose, throat, and tongue operations with hemorrhage in which it is highly important that the reflexes should return rapidly. Boyle (Proc. Roy. Soc. Med., viii, Sect. Anes., 15, 1915) urged the advantage of the patient's seeing the anesthetist a day or 2 before operation, so that he might have a better knowledge of the patient's condition. He had witnessed the use of morphine, atropine, and scopolamine in a war hospital. It added greatly to the comfort of both the soldiers and surgeons, the only drawback being the extreme thirst and dryness of the throat. MISCELLANEOUS FACTORS— fright. — Badly frightened patients, accord- ing to Scholz (Beit. z. klin. Chir., June, 1914), are inclined to tachjcardia, false angina pectoris, polyuria, glj'cosuria, nerv- ous diarrhea, transient numbness, angio- neurotic edema, shallow, rapid breathing, with occasional deep breaths, tremor, pal- lor and dryness of the mouth. Carbon dioxide seems to be a special product of extreme dread. The blood-pressure in such patients suffered a constant and regu- lar decline as the ether or chloroform was administered, until consciousness was en- tirel}' lost; the patient is exposed to vari- ous dangerous reflex processes, especially to reflex syncope from irritation by the anesthetic of the terminals of the trigem- inus in the nose, the reflex action from this involving the vagus terminals in the heart and the respiration center in the medulla. This can be warded off by cocain- izing the nose. The fatalities as general anesthesia is just commenced are un- doubtedly due to this dangerous reflex. The whole secret is to tranquilize the patient, avoid anything suggesting force, and refrain from beginning to operate too early. Persons with marked dread of the operation are exposed to peculiar dangers at the first whiffs of the anesthetic. Breathing Test to Ascertain Condition of Heart Muscle. — General anesthesia is par- ticularly dangerous to persons suffering from myocardial changes, a condition which does not permit of ready recogni- tion. W. A. Schtange (Roussky Vratch, Jan. 18, 1914) found that while a healthy person can suspend breathing from 30 to 40 seconds, owing to the vigor of the heart muscle, in persons with weak hearts the time is shortened to 20 or even 10 sec- onds. The patient, seated in a chair, is told to take a moderately deep inspiration, and, with the mouth closed, to hold his breath as long as he can. The shorter the time the patient can suspend breathing, the greater the danger of an anesthetic, the latter being contraindicated if the time is less than 20 seconds. Pre-ancsthetic Diet. — Opie and Alford (Jour. Amer. Med. Assoc, Mar. 21, 1914). in a series of experiments upon animals, using chloroform as an anesthetic, and employing fats and meats as well as car- bohydrates as foodstuffs, found animals which received carboh3'drates survived; whereas all of those which received meat and fat died. The use of fats increased the susceptibility of the liver to necrosis of chloroform, while a carbohydrate diet seemed to protect the liver from this disaster. Postoperative Analgesia. — Postoperative analgesia recommended by B.Van Hoosen (Boston Med. and Surg. Jour., clxxx, 556, ANESTHESIA. 645 1919), to secure painless convalescence for after recovery from the more urgent surgical patients: Morphine, i/j2 grain symptoms of shock, ether, though un- (0.002 Gm.). and scopolamine, V^oo grain likeh^ to cause pulmonary conditions or (0.0003 Gm.), are given every 4 hours by vomiting when warmed, produces a dan- hypodermic injection for 24, 36 and, in gerous and prolonged lowering of blood- very painful cases, 48 hours after opera- pressure. The most satisfactory results tion. In 452 cases so treated the effects are obtained with nitrous oxide and oxy- werc found to be most beneficial to both gen combined with local infiltration of the patient and nurses. The method greatly region of the incision, particularly in decreases complicating stomach symp- abdominal operations. toms, shortens convalescence, prevents Post-ancsthctic Into-xication. — During an- dread of future operations, and facilitates esthesia the reserve of glycogen in the the work of the nurse. For the first 2 system is rapidly consumed, and if this days after operations, the patients had not supply were replenished by the adminis- only marked analgesia but also some tration of glucose to the patient, the pos- amnesia. sible harmful consequences of anesthesia Trendelenburg Position as Source of Dan- could be in a large measure avoided. gcr. — In MacCardie's opinion (Proceed. Chauvin and Oeconomos (Presse med., Roy. Soc. of Med., Sect, of Anes., Apr., Dec. 18, 1912) administer it as prophylactic 1914), anesthetics have frequently been in the follow'ing form: blamed for complications which are really t> r-i = /icnr- \ ^ ■'Iff. Glucose 5v (150 Gm.). niduced by the Trendelenburg posture, es- ^- , r , r ■ • •' I'lcturc of nnx pecially when the angle of niclmation has • ••• ,,ir \ , , ,r , T. . 1 vomica mvnj (U.5 c.c). exceeded 45 degrees. it not only pro- t-- . jr • • , , , -' mcturc of cinna- motes copious venous hemorrhage, and , , -, n ^ ^ , ., . , mon ntxlv (3 Gm.). embarrasses pulmonary ventilation, but ,,/ . , , , ,. . , . , , Water, enough to also puts an additional strain on the heart. , - , ^,^-, . , ., ^ . . , . , make 5x (300 c.c). Likewise it seems to be an important fac- tor in the occurrence of post-operative pneumonia and bronchitis; and Zweifel Where post-anesthetic intoxication is al- holds it occasionally responsible for post- ready established, glucose should be freely operative intestinal obstruction, surgical administered by mouth, rectum, and even emphysema, apoplexy and acute dilatation intravenous injection. As in diabetic coma, of the stomach. alkalies should also be given. Shock During General Anesthesia.— F. C. Post-anesthetic Vomiting.— Renton (Brit. Mann (Trans. Amer. Med. Assoc; N. Y. ^led. Jour,. Dec. 6, 1913) advises to raise Med. Jour., June 16, 1917) states that the the head of the patient's bed 12 inches, most common of its causes is free hemor- on blocks, leaving it in this position rhage. All persons do not react similarly (Fowler's) 24 to 36 hours, to loss of blood. Trauma to the viscera E. M. Barker (Brit. Med. Jour., Jan. 10, is a common cause when accompanied by 1914) recommends the application after loss of circulatory fluid in the traumatized anesthesia, of eau de Cologne on a mask areas. Excessive nerve irritation is prob- immediately, and allow patient to inhale ably of rarer occurrence than clinical re- tliis for half an hour after being placed in ports indicate. In cases of fractures and bed, the Cologne-water being renewed as trauma to large areas of fat, pulmonary required. fat embolism might act as cause. The I'ontiting. — D'Arcy Power (Pract., July, ductless glands, particularly the adrenals, 1920) states that when vomiting is not are sometimes factors, possibly as primary very severe, sips of hot water may be active agents or owing to the low blood- given. In more persistent cases 15 grains pressure and the changes incident to the (1 Gm.) of sodium bicarbonate may be condition itself. Deep etherization may dissolved in a tumblerful of hot water; the produce most of the symptoms of shock. patient vomits it directly, but the sickness A. Bowlby (Lancet, Jan. 17, 1920) notes afterwards subsides. In very severe cases that where anesthesia must be used shortly give nothing by mouth, but administer a 646 ANESTHESIA. sedative enema, consisting of potassium bromide and chloral hydrate, of each 20 grains (1.3 Gni.), and mucilage of starch, 2 ounces (60 c.c). Wlun vomiting has been unduly prolonged it is sometimes a good plan to feed the patient solid food rather than to restrict him to "slops." C. J. Larkey (Jour. Med. Soc. of N. J., xiv, 8, 1916) attributes post-anesthetic vomiting to the acidosis (q. v. this volume) which follows the physicochemical com- bination of the anesthetic with the lipoids, a process followed in hernia by increased acidity of the cell content and increased capacity for water. To prevent acidosis the preoperative preparation should in- clude a regular diet with plenty of starchy foods up till noon of the day before oper- ation, tlien a supper of cereals, milk with albumin, water, and sugar. If acetone is present in the urine the proteids should be cut down and the carbohjdrates in- creased. Water containing calcium is use- ful, while the administration of sodium bi- carbonate and lactose, 1 dr.ini (4 Gm.) of each every 4 hours for 48 hours before operation is advisable. Following opera- tion the patient is given a 5 per cent, solu- tion of anhydrous dextrose i)y the drip method per rectum, using 250 c.c. (8 ounces). Untozi'ard Effects of AdreuaUn. — Levy (Brit. Med. Jour., Sept. 14, 1912) found that adrenalin exerted a very pronounced cardiac effect in chloroformed subjects. Within a few seconds, injection of 5 minims (0.3 c.c.) of the 1:1000 solution caused pulse acceleration and a raised ten- sion; it became more rapid and was less readily felt owing to diminished excursion. It may, or may not, be perceptiblj- irregu- lar at the wrist; a few temporary pauses were noted, and then the heart suddenly ceased beating; the pupils dilated widelj', and intense pallor supervened. Respira- tory phenomena followed; a few deep breaths were taken, and the respirations ceased also. The writer concludes that it is unsafe to inject adrenalin into the veins or vascular tissues of a patient lightly un- der the influence of chloroform. It may be safely injected just previous to the in- duction, however, or into a patient fully under chloroform, or into a patient anes- thetized to any degree with ether. In the case of light chloroform anesthesia the risk taken is unjustifiable. [The injection of adrenalin into the veins is dangerous under any circum- stance. S.J Depree (Brit. Med. Jour., Apr. 26, 1913) observed sudden death from cardiac ar- rest after the injection of 5 minims (0.3 c.c.) of a 1:1000 solution of adrenalin in the nose of a patient who had been anes- thetized with chloroform. At the time of the injection anesthesia was light, the cor- neal reflex being brisk, and no more chlo- roform was given. All attempts to resus- citate the heart failed. NARCOANESTHESIA.— This term is used by Henry Beates (N. Y. Med. Jour., Jan. 13, 1917) to identify a method which is asserted to have secured unconscious- ness and perfect freedom from pain and exert a minimum of injurious effects. About 2V:i or 3 hours before the opera- tion, the patient receives a hypodermic in- jection of Vr.o grain (0.0013 Gm.) of scopo- lamine hydrobromide and % grain (0.01 Gm.) of morphine. One-half hour later, a second injection is administered and an hour later a third, which may or may not contain morphine, as the susceptibility of the patient is more or less apparent. At the time of the third injection an enema of 2 fluidounces (60 c.c) each of whisky and spiritus aetheris compositus is given. By the time the hour for the operation has arrived, the patient is, as a rule, in a con- dition of complete narcoanesthcsia. The face is more or less flushed. Occasionally there is moderate pallor. The respirations resemble those of profound sleep and, be- cause of the morphine and the suscepti- bility of the patient to its action, there may be a retardation of the respiratory rate to as low as 10 or 8 to the minute. There has been no material disturbance ot the renal functions observed in any case; this suggests that even with the coexist- ence of renal degenerative lesions narco- anesthcsia is safe. Operations upon the biliary tract, herniae, appendicectomies, pelvic operations of major t3'pe, such as hysterectomy, plastic work in the pelvic canal, operations upon the kidneys and rectum, constitute a group that may be most admirably subjected to narcoanes- thcsia and performed with the leisure ANESTHESIA. 647 necessary for thorough surgery. One im- portant precaution is the patient must never be left alone, or without an intelli- gent attendant, as there is danger of strangulation. Dr. Wayne Babcock sug- gests the placing of a wisp of cotton to the nostril, which serves as an indicator of the ingress and egress of breath, thus preventing a mistake in considering the convulsive movements of strangulation for those of respiration. The patient sleeps from 3 to 7 hours after the operation and aw-akes often without any discomfort ex- cept slight dryness of the nose and throat. LOCAL ANESTHESIA.— According to R. E. Farr (Amer. Jour. Obstet., Ixxx, 653, 1919), the method of choice in local anesthesia is infiltration when it does not interfere with the anatomical relation of the tissues, but in some cases, hernia for example, nerve blocking is recommended. Abolition of the reflexes of the abdominal wall is the ideal in abdominal operations under local anesthesia. Vertical retraction and great care in the handling of the tis- sues are important points. Eggleston and Hatcher (Jour. Am. Med. Assoc, Oct. 25, 1919) assert that acute intoxication in man from local anesthetics is far more common than is indicated by the number of recorded cases. In over 300 experiments in cats it was found that when large fractions of the minimal fatal doses are injected intravenously at inter- vals of from IS to 20 minutes, or when relatively dilute solutions of the drugs are injected slowly and nearly continuously, the several drugs can be divided into 2 groups as regards rate of elimination. Group 1 includes alypin, apothesin, beta- eucaine, nirvanin, procaine (novocaine), stovaine, and tropacocaine, all of which are rapidly eliminated, so that several times the minimal fatal dose can be injected in the ways just mentioned in periods of 1 or 2 hours without causing death. Group 2 includes cocaine and holocaine, which are much less rapidly eliminated and there- fore cause death in much sinaller total doses when given as described. The elim- ination of all the local anesthetics is ac- complished almost entirely by their de- struction in the liver. Epinephrin and artificial respiration should prove effective as a resuscitative measure in many cases of acute poisoning in man. To diminish the likelihood of in- toxication from the "subcutaneous injection of local anesthetics in man, epinephrin should always be added to their solution. Novocaine (procaine) being the safest anesthetic known, a inore dangerous drug should not be used, according to Farr (Trans. Amer. Med. Assoc; Med. Rec, May 15, 1920). Many children are in a bad condition follovving the use of a gen- eral anesthetic, and the nature of the an- esthetic often decides the issue. A child can be restrained on an arm table set at right angles to the operating table. The feet are attached by bandages to the oper- ating table, and the nurse holds the arms above the elbow. As a rule the child needs restraint only while the anesthetic is being given. One should alwaj's be prepared to reinforce the local anesthesia with general anesthesia; but it is rarely necessary. I'^arr refers to a series of 129 cases of chil- dren operated under local anesthesia and in only 9 of whom there was any pain; when this occurs it is due to an error in technique. COMPARATIVE MERITS OF VA- RIOUS LOCAL ANESTHETICS.— G. MacGowan (Calif. State Jour, of Med., Jan., 1916) holds that a local anesthetic to be valuable must not of itself be a cause of pain, either before its action is estab- lished or after it has ceased. None of the drugs are used pure, but all need to be dissolved in fluids isotonic with the juices that bathe the body cells, such as a 0.9 per cent, solution of common salt. Cocaine, the first local anesthetic to be discovered, has been abandoned because of its dis- advantages except in e3'e and nasal sur- gery, and sometimes in urethral opera- tions where the newer and safer anes- thetics are inactive. Tropacocaine is the ideal agent for spinal anesthesia. Beta- eucaine does not differ widely from co- caine; as a protoplasmic poison, it pro- duces the same symptoms, but the dose required is greater. It is slightly less powerful as a local anesthetic, does not diffuse so well, and is more irritating. Its solutions are stable and can be sterilized by boiling. Acoin is a dangerous poison, and is decomposed readily by alkalies. Holocaine anesthetizes the eye without 648 ANESTHESIA. dilating the pupil, producing dryness of the cornea, or preventing bleeding. Chlo- retone or anesol is very irritating. Ortho- form, anesthesin, subcutin, propesin, and 2yklcform are all slightly soluble powders with anesthetic properties when brought in contact with exposed nerve filaments or endings. They arc used upon the skin in dusting powders or salves, in the rectum or vagina as suppositories or salves, and are also useful in the nose, throat, and in- testinal tract, especially the stomach. The most efficient of the group is anesthesin, over which the others possess no advan- tages. Stovaine has been recommended for spinal anesthesia, but is irritating and painful for infiltration anesthesia. In a 1 per cent, solution it is useful as a local anesthetic when used by instillation for an instrumental examination of the urethra and bladder. Alypin is a close relative of stovaine, is readily soluble in watery solu- tions, is less active and more irritating than cocaine when used hj'podermically, and its toxic symptoms are similar to those of the latter. Novocaine is but feebly poisonous, its watery solutions up to 10 per cent, are not irritating; it may be sterilized and resterilized without marked efTect upon its anesthetic proper- ties, which are greater than those of any other drug used for local anesthesia, when combined with suprarenine, with the ex- ception of cocaine. It can be applied pure to the cornea and to frcshl}- denuded sur- faces without causing pain or subsequent edema. For infiltration anesthesia isotonic solutions of \-i, 1, 2, and 4 per cent, are the most useful; greater concentrations are not necessary and should not be used, even though it is only feebly toxic. Hydro- chloride of quinine and urea in watery solutions of from 0.25 to 1 per cent, causes the formation of a fibrinous exudate in tissues infiltrated with it, which delays the healing of wounds. Tetanus has been ob- served after this salt has been used. Its one valuable quality is the length of time its anesthetic effects last, sometimes for many days, on account of which it may be used to inhibit pain in intense and per- sistently localized neuritis, and in blocking the sensation of itching in circumscribed and chronically thickened patches of eczema. Benzyl alcohol was found by the writer to be a fairly efficient anes- thetic for intact mucous membranes, greatly surpassing procaine, ranking about with alypin and betaeucaine, and somewhat weaker than holocaine or cocaine. Its action is not as last- ing as that of -cocaine, and even 1 per cent, solutions produce much smarting. Sollmann (Jour. Pharm. and Kxpcr. Thcrap., Juh', 1919). ANESTHESIA ACIDOSIS.— In gath- ering data to indicate the character of the operative risk, it has been customarj' for a long time, as stated by H. Morriss (Jour. Amer. Med. Assoc, May 12, 1917), to em- ploy uranalysis, blood counts, hemoglobin determinations and estimations of the ar- terial tension. It seems advisable often to add to these the determination of what has been called the "alkali reserve"; for postoperative nausea and vomiting, menacing convalescence, may depend on an acidosis for which the anesthetic is responsible. Under normal circumstances the acid-base equilibrium is remarkably stable. The* mechanism involved in the maintenance of the equilibrium comprises: (1) the elimination of carbon dio.xide by the lungs; (2) the excretion of acid salts by the kidneys and sweat glands; (3) the presence of "buflFer" substances in the blood which include the bicarbonates, phosphates, and probably proteins; (4) the production of ammonia at the expense of urea, and (5) the influence of the baro- metric pressure (oxygen tension) to which the individual is accustomed, a factor as 3 et imperfectly understood. It has been demonstrated that the lungs take a leading part in the regulation of the acidbase equi- librium of our bodies. The carbon dioxide which the lungs excrete has acid proper- ties; when in the blood it is neutralized through combination with alkali. The excess of available alkali is termed the alkali reserve. This may be estimated in- directly by the determination of the car- bon dioxide in the alveolar air, or of the capacity of the blood plasma to combine with carbon dioxide. In anesthesia there results a com- pensated acidosis in from 30 to 85 per cent, and an uncompensated acidosis in from 15 to 20 per cent, of cases. ANESTHESIN. 649 The protection of the patient from acidosis rests in Hmiting suboxida- tion and in supplying the body with alkah. The acids are usually neutral- ized as the}' are formed by sodium bicarbonate, ammonia, and less easily mobilized bases, such as calcium and magnesium. The symptoms vary from headache, nausea and vomiting, gas pains and mental dullness, to coma and death. The following factors influence uncompensated acidosis: ex- treme age, impaired kidney function, exhausting diseases, prolonged sepsis, duration and depth of anesthesia, hemorrhage, and preoperative fasting. Shock is always associated with un- compensated acidosis. A patient showing before operation a low bi- carbonate content should be given the benefit of alkalinization with sodium bicarbonate, though further studies may show the use of mag- nesium and calcium to be equally im- portant. Too much alkali may do harm; therefore, a second analysis 2 hours after alkalinization should be made, to ascertain whether the de- sired result has been attained. S. P. Reimann (Trans. Amer. Assoc, of Anesthet. ; Jour. Amer. Med. Assoc, Aug. 2, 1919). ANESTHESIN. -Anesthesin is, chemicalh% ethyl para-aminobenzoate [Co- H4.NH2.COOC2H5]. It occurs as a white, odorless, and tasteless powder, almost in- soluble in cold water, with difficulty solu- ble in hot water, sparingly soluble in fatty oils (2 to 3 per cent.) and in dilute glyc- erin, easily soluble in alcohol, ether, chlo- roform, benzene, and acetone. It melts at 90° to 91° C. Though decomposed by prolonged boiling, it can be rendered sterile without deterioration when dis- solved in oils. Alkalies and alkaline car- bonates are incompatible with it, remov- ing the ethyl group to form alcohol and setting free para-aminobenzoic acid. PHYSIOLOGICAL ACTION.— The most conspicuous feature of anesthesin is its local anesthetic property. The drug differs radically from cocaine in that it is but very feebly toxic and is insoluble in water. The low toxic power was shown in the experiments of Binz, who adminis- tered 0.6 Gm. (10 grains) of the drug in 20 c.c. of oil by stomach tube; on the next day the animal was in good health, with urine normal. The dose required to kill was found to be 1.15 Gm. (18 grains) per kilo of animal, the symptoms produced being paralysis, gradual loss of sensibility in the hind limbs, and dyspnea terminat- ing in asphyxia. The drug was also ad- ministered intravenously in dogs and in- tiaperitoneally in guinea-pigs, with simi- lar results indicative of a low degree of toxicity. The intoxication produced by anesthesin is in some ways comparable to that of acetphenetidin; massive doses lead to the formation of methemoglobin, with conse- quent methemoglobinuria. Anesthesin placed upon the tongue pro- duces a feeling of numbness in two to three minutes. By virtue of the insolu- bility of this substance, its anesthetic action is more strictly localized than that of cocaine. It is also feebler, but is more enduring. It is said to exert no action on the vessels at the site of application, caus- ing neither vasoconstriction nor vasodila- tion. Over orthoform it has the advan- tages of being more stable and practically non-irritating. THERAPEUTIC USES. — Internally, anesthesin, as first demonstrated by von Noorden, is useful in conditions of gastric hyperesthesia, including nervous dyspep- sia and gastric ulcer. The dose is 0.2 to 0.5 Gm. (3 to lYi grains) ten to fifteen minutes after the ingestion of food. In laryngeal tuberculosis an insufflation of anesthesin lias been found by Courtade to arrest the severe pain and, therefore, the dysphagia for nearly forty-eight hours. Earp found it very useful in very painful bleeding external hemorrhoids. The bow- els were moved freely by enemas, hot ap- plications were used freely, and the fol- lowing ointment was applied twice daily: R Anesthesin 15 grs. (1 Gm.). Ergoliii 1 dr. (4 Gm.). Ichthyol 30 mins. (2 Gm.). Lanolin 3 drs. (12 Gm.). Petroleum ..to make 1 oz. (31 Gm.). Earp also found anesthesin useful in perineal eczema which had not yielded to other measures. S. 650 ANEURISM (BABCOCK). ANEURISM. —DEFINITION.— An abnormal circumscribed blood- tumor containing a cavity communi- cating with an artery. An aneurism consists of a sac, neck, and contents. The contents include liquid blood, co- agula, and laminated fibrin. Aneu- risms vary in size from that of a millet seed to that of a child's head. In order of frequency aneurisms involve the thoracic aorta, popliteal artery, fem- oral artery, abdominal aorta, subclavian artery, innominate artery, axillary artery, iliac artery, and the cerebral and pulmonary arteries. VARIETIES.— Congenital. — Con- genital aneurisms are extremely rare, but they have been reported involving the abdominal aorta and ductus Botalli. A rare congenital deficiency of the elastic elements of the walls of the arteries may be the cause of multiple aneurisms, especially involving the smaller arteries of the body. Idiopathic. — Idiopathic aneurisms are those arising without obvious traumatic injury to the vessel wall. They are usually dependent upon dis- ease of the artery, and constitute most of the aneurisms involving the great vessels of the trunk, and the smaller aneurisms of the brain and other viscera. Traumatic. — Traumatic aneurisms are those resulting from mechanical in- juries sustained by the arterial wall, either in the form of a contusion, in- cision, or laceration. Hernial. — Hernial aneurisms are usually small traumatic aneurisms pro- duced by the bulging of the inner tunic through the divided outer layers of the arterial wall. True. — True aneurisms are those having walls formed by the normal coats of an artery. It is rare, however, to find an aneurismal sac in which in- tima, media, and adventitia can all be demonstrated. False. — False aneurisms are those in which the sac is formed by tissues other than those derived from the w all of the artery. They follow arte- rial incisions or ruptures, but even with these false sacs the endothelium proliferates from the intima of the artery into the sac and finally tends to line it. Diffuse. — Diffuse aneurisms are false aneurisms resulting from an ex- tensive extravasation of blood from an open artery. As a rule, they are due to traumatism, but they also re- sult from the spontaneous rupture of a diseased artery. Dissecting. — Dissecting aneurisms are those in which the aneurismal sac lies between the coats of the artery. As a rule, they have two mouths, the blood entering through one opening, separating the layers of the arterial walls, and then, at some distance, re- communicating by a second opening with the arterial stream. These oc- cur most frequently in the abdominal aorta and may produce a very exten- sive separation of the arterial coats. Embolic. — Embolic aneurisms are those resulting from the lodgment of emboli. By some they are attributed to the laceration of the walls of the small vessels by calcareous embolic particles. It is evident that they may also result from degenerative or inflammatory changes of the arterial wall, secondary to the lodgment of the embolus. Embolomycotic aneurisms develop during the course of endocarditis and occasionally during some of the acute infectious diseases, which form a dis- tinct group by themselves, differing in pathogenesis, clinical course, and prog- nosis from those developing secondary ANEURISM (BABCOCK). 651 to chronic arterial changes. They have been recognized since 1851. They may develop in one of three ways. Most commonly they follow an endarteritis associated with lodgment of infected emboli at the bifurcation of arteries. A few cases have been reported which developed during the course of infec- tious diseases unaccompanied by endo- cardial changes. The possibility of traumatic origin is also supported by the observation of Ponfick and Thoma of calcified emboli in the arterial wall and projecting into the aneurism. Clinically, embolomycotic aneurisms dif- fer from those following chronic arte- rial changes: (1) in developing at an earlier age ; (2) in frequently being multiple, acute and chronic forms often occurring in the same individual : (3) in the frequent involvement of visceral arteries, and (4) in the tendency to remain small. A number of cases have been reported in which no satisfactory explanation is given of the cause. About one-fourth of the cases observed developed during the third decade of life, and about one-fourth during the second. They are much more frequent in males, although the authors have been unable to demonstrate the reasons for this satisfactorily. They have collected, including their own cases, 96 aneurisms of this class occurring in 65 patients, they frequently being multiple, and re- port 3 cases observed by themselves. The largest proportion of these aneu- risms occurred in the superior mesen- teric and cerebral arteries, and in the aorta, which is in marked contrast to the distribution of the ordinary type of chronic aneurisms, which rarely occur in the superior mesenteric or cerebral arteries. There is nothing characteristic in the symptoms, and they are not often suspected until fatal ab- dominal or cerebral hemorrhage occurs. Bacteria have been found within the wall of the aneurism, showing the bacteriological relationship between the vegetations on the heart valves and the clot in the aneurism. The forms are usually the streptococcus and staphy- jococcus, though other species have been reported. In 2 of the author's cases, examinations revealed the pneumococ- cus. This infection of the aneurisms complicates any operation, the patients being usually in a critical condition and not enduring surgery well. Dean Lewis and V. L. Schrager (Jour. Amer. Med. Assoc, Nov. 27, 1909). Miliary, — Miliary aneurisms are very minute aneurisms most fre- quently observed in the brain or lungs. They involve small- or me- dium- sized arteries and often occur in great numbers. Fusiform or Ectatic. — Tn these forms the weakened arterial walls yield in every direction, forming a fusiform, or, rarely, a somewhat C3lin- drical, enlargement. The three coats of the artery may be demonstrated' in the sac ; usually there is little clot present, and there may be few symp- toms, unless through weakness of a part of the wall a sacculated aneurism follows. The walls of the fusiform aneurism may be thicker than that of the adjacent artery. Sacculated. — Sacculated aneurisms are due to the bulging of one side of an artery. The elastic and muscular layers of the artery are not found in the walls of the sac. ETIOLOGY. — Aneurisms result from conditions weakening the ar- terial wall and increasing the blood- pressure. Race. — The Anglo-Saxon race is most frequently affected ; the English more than the American, a condition attributed to the greater consumption of alcohol in England. Aneurism is rare in the Asiatic races and in Italy. It is three times as prevalent in the American negro as in the white race. Age. — Aneurism is most frequent be- tween the ages of 30 and 50, a period when degenerative changes in the ar- 652 ANEURISM (BABCOCK). teries are especially found in those engaged in laborious physical work. Sex. — Men are affected ten times as frequently as women, excepting the carotid and dissecting forms of aneu- rism, which occur more frequently in women. The more laborious occupa- tions of men and their greater tendency to dissipation and excess explain the in- fluence of sex. Soldiers, sailors, athletes, cab driv- ers, furnace men, and others engaged in violent, but intermittent exercise are especially predisposed to aneurism. It is eleven times more frequent in the English army than in the civilian, and is much more frequent in soldiers than in sailors, a condition attributed to the pressure and strain from poorly fitting clothing and heavy accoutrements. Cab drivers, apparently from the pull upon the arms, are especially susceptible to thoracic aneurism. \'essels at the point of flexion and extension, such as the popliteal and iliacs, or under greater strain, such as those of the right arni rather than the left, are more frequently involved. Oc- casionally symmetrical aneurisms, as double popliteal aneurisms, occur. Those conditions that produce a weakening of the arterial wall, espe- cially all the causes of arteriosclerosis and atheroma, are important predis- posing causes to aneurism. These in- clude syphilis, alcoholism, rheumatism, gout, and the action of mineral poisons like lead. Arterial disease appears to be rare, almost unknown, in animals. Syphilis, being probably peculiar to man, is by this observation placed more firmly in the list of etiological factors. Arterial disease in children under 6 years, even in those who are victims of congenital syphilis, is practically unknown. In those from 6 to 15 years it is rare. It is found in the initial stage most com- monly between the ages of 30 and 40 years. The teratological factor, though an undeterminable one, is of great im- portance. Arterial disease seems to be attributable to syphilis in about 32 per cent. , to tuberculosis in about 16 per cent. The facts presented go to show that the colored race is affected about four times more frequently than the white. General arteriosclerosis seems to be not commonly found with aneurism, and its presence may be considered as evi- dence against the probable development of aneurism. Staining with selective stains and treating with a chemical which digests tissue show the elastic tissue to be free of histological alterations, sug- gesting that this tissue undergoes physi- cal or molecular rather than histological change. C. N. R. Camac (.\mer. Jour. Med. Sci., May, 1905). The influence of rheumatism is one of great importance, especially in young patients. The writer, working with Renon, has recently published some im- portant observations relative to this subject. According to the cases col- lected by this author, the average age is from 10 to 16 when the patients have usually had several attacks of acute rheumatism. Repetition of the disease is regarded as an essential factor. The appearance of aneurism is preceded for some time by the signs of aortic in- competence and hypertrophy of the heart. After a period of considerable latency, the symptoms and signs of aneurism appear rapidly. They are dyspnea, especially marked after effort, and characterized by forced inspiration without actual oppression. After a short time this dyspnea becomes per- manent, though occasionally varied by pseudoasthmatic crises, sometimes at- tacks of pain resembling angina pec- toris. The attacks usually appear dur- ing the first sleep. The patient retires to rest in his ordinary condition, but suddenly awakes in great agony, com- plaining of a feeling of constriction in front of the chest, air hunger, desire to cry out, and violent inspiratory efforts are made. The crisis may last ANEURISM (BABCOCK). 653 from a quarter to one hour, and then gradually disappear. Occasionall}' the crises are entirely painful without respiratory trouble. Considerable in- tervals maj' elapse between them, for in one case quoted by the author they numbered 2 or 3 during the 3'ear; in others they are more fre- quent, occurring once a month, or even dailj'. The diagnosis is con- firmed by the rapid appearance of physical signs. These aneurisms, as a rule, affect the upper right costal area, and do not differ from those usually observed in other cases. Aortic aneurism in young rheumatic subjects may develop fully in the course of a few weeks, sometimes in succeeding stages corresponding to the rheumatic crisis. After each crisis there may be temporary im- provement, due to retrocession of the tumor. This improvement is re- versed by a fresh crisis of articular inflammation. The condition is, there- fore, progressive, and there is little hope of obliteration taking place in the sac. Prognosis is usually fatal, death often occurring suddenly either from hemorrhage or angina pectoris. Feytaud (These de Paris, 1906). The writer obtained a history of syphilis in over 11 per cent, of 34 cases of aortic aneurism at the Hel- singfors Hospital since 1900. In the 10 tested for the Wassermann re- action, it was positive in 90 per cent. The shortest interval since infection was 7 years, the longest 35. The youngest patient was 30 at the time of his death, the oldest 70. In 9 cases rupture of the aneurism was the cause of death, and in 13, inter- ference with the action of the heart. In all but 2 cases the aneurism was in the thoracic aorta. Sjoblom (Fin- ska Lakare Handl., Iviii, Xo. 5, 1916). Definite evidences of the rather commonly syphilitic nature of aneu- rism detected. The writer found spirochacta pallida clustered in foci in several cases of aneurism of the thoracic or abdominal aorta. Y. Manouelian (Bull, de la Soc. Med. des H6p., May 28, 1920). Only 5 of the author's 29 patients with aortic aneurism had a history excluding the possibility of syphilis. The outcome was not known in 8 patients, but 9 were still living after intervals of from 16 months to 12 years. Syphilis plus alcoholism is a particularly dangerous combination. Martinet (Presse med., Oct. 16, 1920). Cardiac hypertrophy, plethora, and renal disease are also factors. Exper- imentally, aneurism may be produced by the repeated introduction of adren- alin into the circulating stream. PATHOLOGY.— Idiopathic aneu- risms develop in an area of atheroma, in the situation of an old scar, the point of lodgment of an embolus, or other weak area in the arterial wall. All forms of aneurism are lined by endo- thelium, excepting the fusiform aneu- risms ; the media of the artery does not constitute a layer of the abnormal sac. This means that the normal muscular and elastic coats are absent, and that the vasa vasorum upon which the arterial wall depends for its nourishment is lacking. The sacs of all saccular aneurisms thus tend to be weak while blood-pressure causes them gradually to distend. In the fusiform aneurism all the layers of the arterial walls may remain and the wall of the sac may be thicker than that of the normal artery, the in- tima being thickened by atheroma, the adventitia by the deposit of fibrous tis- sue, while the middle coat is thinned. As the inner coats of an artery consti- tute not less than three-fourths of the thickness of its wall, containing the elastic and muscular layers, and also the vasorum supplying the walls with nourishment, the thinning, ab- sence, or damage to these structures means a weak and poorly resilient wall for the aneurismal sac. 654 ANEURISM (BABCOCK). In sacculated aneurisms there is usually a progressive deposit of layers of fibrin against the wall of the sac, tending to strengthen the walls and to lessen the fluid contents. The lessen- ing of the fluid contents is important, as the pressure on the sac wall varies as the square of the diameter of the cavity which contains the fluid. At times the blood-clot is deposited in progressive layers until the entire sac is filled, resulting in a spontaneous cure. The blood-clot at the periphery is white, laminated, and fibrous, al- though rarely organized into the true fibrous tissue, the lack of vasorum pre- venting vascularization. The aneurism, therefore, may consist of a sac or body, which in the sacculated form may com- municate by neck and opening with the artery. The sac is strengthened on the outer side by the deposit of fibrous tis- sue, an evidence of the reaction and irritation of the tissues against which the aneurism presses. The sac may contain peripherally white, laminated clot ; then a layer of softer, red Mood-clot, and finally fluid blood communicating with the blood- stream. In the cylindrical and fusi- form aneurisms little or no lining clot may be present. The size and shape of the sac are modified by adjacent pressure. Rota- tion of the sac may occur so that in a fusiform aneurismal sac the orifices of the efferent and afferent trunks may lie at the sides or at the equator of the sac, rather than at the poles. Matas classifies aneurisms by the number of orifices which connect them with the parent artery. These orifices may only be accurately determined af- ter the opening of the sac. Fusiform aneurisms have two distinct orifices ; saccular or sacciform aneurisms are those which are connected with the lumen of the parent vessel by a single circular, ovoid, or elongated opening through which the blood flows in and out the sac. The sac of the aneurism may have many collateral branches corresponding somewhat with the branches normally given off by the segment of the arterial wall forming the aneurism. These collat- erals may be functional or impervious and containing thrombi. The perianeu- rismal circulation may be very impor- tant in maintaining the collateral circu- lation after operation upon the sac. An aneurism influences the blood-stream, absorbing the cardiac wave, so that the pulse distal to the sac is delayed and weakened. To compensate for this the heart may hypertrophy and anastomotic channels form. The aneurism may so press upon the main vessels as to completely inter- rupt the circulation beyond the sac. The adjacent tissues are variously affected. Bone is eroded and pro- gressively destroyed by the continuous ])ressure, cartilage being much more resistant than bone. Nerves are stretched, compressed, and flattened, at times destroyed, giving rise to paresthesia and more rarely paralysis. Adjacent veins may be com- pressed with the production of cyano- sis and edema, and rarely erosion and perforation in the venous channel occur. Mucous canals are compressed and displaced, while fibrous tissue, ten- dons, and fascia are flattened, stretched, and often incorporated into the sac. Thrombi may form in tributary ves- sels, and emboli may result from the dislodgment of clot or fibrin. Cerebral complications, such as hemiplegia, in- farcts in the internal organs, and gan- grene of the extremities, also occur. ANEURISM (BABCOCK). 655 SYMPTOMS.— Aneurismal dilata- tion may occur suddenly from trauma- tism or a great increase of intravascu- lar pressure and may be characterized by sharp pain and rapid enlargement along the course of an artery. The sac, however, usually forms slowly and' at first without pain or any other symptom. Case of a woman aged 42 years, attended by remarkable features. The aneurism was eroded and perforated the sternum in two places without ever causing pain or any other pressure symptoms ; it presented externally as a tumor, and then disappeared under treatment by iodide of potassium, the skin rupturing without letting out any blood. This series of events was re- peated several times in the course of seven years. Death occurred from the sudden bursting of the aneurism as the patient lifted a pitcher of water. R. C. Cabot (Amer. Jour. Med. Sci., April, 1900). The diagnosis of aortic aneurism still remains in obscure cases a difficult one, and even the X-ray examination may be misleading. Attention called to the frequency with which, in aneurism of the arch, the left supraclavicular groove is obliterated or even bulges, and the left external jugular is obviously fuller than the right. The anatomical reason lies simply in the compression of the left innominate vein as a result of the dilated arch. A mediastinal tumor may have the same effect, but dilatation in cases of aortic insufficiency is apparently seldom sufficient to effect compression. Dorendorff (Deut. med. Woch., Nov. . 31, 1902). Pain is one of the earliest and most constant symptoms of aortic aneurism. It was the first and most severe symp- toms in about half of the author's cases. It is possible that it should be absent, though there may be dyspnea, cough, and cyanosis, and though the sac may perforate the chest wall or erode the spine. The most common situation for the pain is in the region of the heart itself, radiating to the neck, the shoulder, and back, and down the left arm or both arms. In some cases the abdominal pain is severe. Several distinct varieties of pain may be recognized in this disease : 1. At- tacks of true angina, having paroxysms of pain of maximum intensity, with radiation to the arm. 2. Sharp neu- ralgic pain due to pressure on the nerves, perhaps extending along the course of the nerves, and associated with herpes when the descending tho- racic aorta is implicated. It is similar in character to that which is caused by the pressure of pelvic tumors, and by disease of the vertebrae, and it may be paroxysmal in character. 3. Pain of a dull, boring character which is present when the chest wall or the spine is eroded by the aneurismal sac. This is the form of aneurismal pain which is most enduring and most severe. It is due to tension and stretching of fibrous and bony structures rather than to pressure upon nerve cords. 4. Pain re- ferred to the nerves of the arms or the skin in the precordial region or to the pectoral or sternomastoid muscles. One object of the writer's paper was to narrate types of cases in which at- tacks of angina pectoris customarily precede the appearance of the aneurism for months or years. The paroxysms may not be in the least suggestive of aneurism, but they are associated with- early structural changes in the wall of the aorta. In sclerosis of the aorta pain is not necessarily a symptom, the author having observed this fact in syphilitic patients. With lesions of arteries the pain may be the »iost in- tense, this being frequently observed in embolism, thrombosis, and the ligation of vessels. W. Osier (Med. Chronicle, May, 1906). With the exception of the rare cases in which there is trouble with swallow- ing, the early symptoms of aneufism, manifested by pressure, are usually either pain or disturbance with the re- spiratory apparatus. The latter may come either from pressure on the air passages or from pressure on the re- current laryngeal nerve. The symp- toms frequently simulate those of heart 656 ANEURISM (BABCOCK). disease, and their true meaning is learned partly by- not finding a car- diac condition that will explain the symptoms, and partly by looking for and finding evidence of an aneurism. The picture of aortic aneurism in its earlier stages is not uniform, but varies widely with the position and size of the aneurism. There are no pathognomonic signs. Yet a careful physical examination and a careful consideration of the physical signs and symptoms should enable the de- tection of the existence of an aneu- rism of the ascending or transverse arch at a very early stage. An early positive diagnosis of aortic aneurism is obtainable only by the X-ray. Expansile pulsation is not constant. Abnormal dullness is a valuable sign when present. The most constant sign is systolic bruit, which was present in 11 of 19 cases. Tracheal tugging occurred in but 2 cases. The earliest and most con- stant symptoms were dj'spnea and cough. Interference with passage of bismuth capsule the size of a quarter through esophagus was found pres- ent in every case tested (by X-rays). This is especially valuable in small aneurisms growing back from the transverse part of the arch, as it shows the esophageal obstruction be- fore dysphagia appears. Lange (Lan- cet-Clinic, Feb. 19. 1910). Only 2 phenomena were present in any considerable percentage of the cases, pain and dullness. The pain may be substernal, vertebral, may ex- tend down either arm or up the side of the neck to the occiput. The pain may be continuous or may occur as typical attacks of angina. Percus- sion seems to yield earlier informa- tion of an intrathoracic growth than any other method of phj-sical exami- nation. Lemann (Amer. Jour. Med. Sci., Aug.. 1916). The writer found 17 cases of aneu- rism of the splenic artery mentioned in the literature. His own patient complained of dyspnea on exertion and edema. The abdomen was dis- tended and tympanitic, with a definite fluid wave and shifting dullness. The temperature varied from 98° to 103° F. Abdominal paracentesis was per- formed, the trocar being inserted in the midline about midway between the umbilicus and pubis. After 1200 c.c. of slightly cloudy, reddish fluid had been withdrawn, the flow stopped. At the second puncture, Vi: inch lower down, the patient at once experienced a sharp pain in the abdomen, and the needle was withdrawn. Patient col- lapsed and died in 3 hours. The nec- ropsy showed a ruptured aneurism of the splenic artery, not due to trauma. Garland (Boston Med. and Surg. Jour., Apr. 14, 1921). The aneurism forms a smooth round or oval enlargement in the course of an artery. It is not sensitive, unless in- flamed, is not adherent to the overlying skin, but may be associated with edema and venous congestion of the parts dis- tal to the tumor. The swelling has an expansive pulsation up to the time that a sufficiently thick layer of clot forms within the sac to abolish this sign, so that the symptoms are at times divided into those of the expansile and those of the non-expansile stage. The artery distal to the aneurism gives a retarded and feeble pulse. The expansile pul- sation may be less marked and the tumor softer when the parts are ele- vated. The pulsation is diminished by pressure upon the main artery prox- imal to the aneurism, and in some cases the sac may then become softer and collapse. On auscultation a systolic or sometimes a double rough murmur or bruit is heard, loudest at the proximal pole. A shadow, emphasized if cal- careous deposits are present, may be shown by the fluoroscope or skiagraph. Subjective symptoms include pain from the stretching and compression of nerves and the arrest of the venous or lymphatic circulation. The pressure and erosion of bone, especially noticed ANEURISM (BABCOCK). 657 in aneurisms of the aorta, cause the characteristic boring, so-called osteo- pathic pains which are usually more severe at night. In the skull the rushing sound and bruit, headache, and the evidences of cerebral pressure or irritation, such as choked disk, vomiting, dilated pupil, motor and sensory disturbances, and localizing nerve palsies, may be present. When an aneurism causes paralysis of the third nerve alone, it is uni- formly seated upon the trunk of the internal carotid, between the origins of the anterior and posterior com- municating arteries. When the aneu- rism involves the origin of the poste- rior cerebral artery, the paralysis of the third nerve is accompanied by paralysis of the corresponding facial. The only subjective symptoms (be- sides the diplopia) are pains in the head and constant noises upon the same side as the aneurism. These cases always end fatally. Pascheff (Archiv d'ophtal., Oct., 1910). In the neck the situation of the tumor, expansile pulsation, and the ef- fect upon the distal vessels are charac- teristic symptoms. In the chest the recurrent laryngeal nerve frequently is involved with the production of rasping voice, spasm or paralysis of the vocal cord, and brassy cough. Pressure upon the sympathetic may produce unilateral sweating and unilateral contraction or dilatation of the pupil as well as tachycardia. Pe- ripheral neuralgia may result from compression of the intercostals. Com- pression of the phrenic may cause dyspnea and hiccough, while pressure upon the esophagus may result in dysphagia. Although there is no one pathog- nomonic sign of thoracic aneurism, there are certain symptoms and signs taken together which make its exist- 1—42 ence practically certain. The pain, often slight and not complained of except after particular inquiry, is continuous, is situated near and to the left of the vertebral column, and tends to radiate to the shoulder, the left arm, and the neck. Examination of the chest shows no loss of reso- nance on the left side, but the reso- nance is not increased as in pneumo- thorax. At the same time the breath sounds are diminished over the left lung — this being due to partial com- pression of the left bronchus. The inspiratory sound is shorter over the left side, the first period of inspira- tion being inaudible and the air then entering with a rush, as though a valve had been opened. On inspec- tion, there is relative immobility of the left side of the chest, or in some cases there may even be definite re- traction. If the above signs be pres- ent, together with dyspnea on effort, in a patient whose general health is fairly good and who has no sign of malignant disease, the presumption of the existence of aneurism is strong. Inequality of the pupils is often an early symptom. Clement (Lyon med., March 31, 1907). In 40 cases of aortic aneurism in- vestigated at the Seamen's Hospital, Greenwich, the blood-pressure on admission was invariably above nor- mal. A difference of 5 or 10 mm. Hg. between the two arms was of little importance, but a marked differ- ence of from 15 to 20 mm. or so was strong evidence of the presence ot aneurism. Mackinnon (Brit. Med. Jour., Oct. 4, 1913). Hemoptysis from perforated aortic aneurism was witnessed by the writer some 15 times owing to tracheal or bronchial perforation, all the cases being necessarily fatal. But with the diagnosis established, hemoptysis may not, however, mean that the aneurism has burst. It may be due to atheroma of the pulmonary ves- sels, or the aneurism itself, still in- tact, may cause a perforation into the pulmonary artery. Hampeln (Deut. med. Woch., May 1, 1913). 658 ANEURISM (BABCOCK). The various pulmonary lesions caused by or associated with aortic aneurism include collapse, bronchiec- tasis, chronic pneumonia, and. rarely, localized gangrenous areas around the bronchi. They are apt to re- semble pleuritic effusion, malignant disease, cirrhosis, and phthisis very closely. In some cases tuberculosis develops in the lung, which is thus collapsed or affected with chronic pneumonia. Bramwell (Edinburgh Med. Jour., Feb., 1916). Tracheal tugging is often found in aneurism of the arch of the aorta, and is due to the transmission of the aneu- rismal pulsations to the left bronchus, and is detected by inclining the head and lifting the larynx and trachea by the finger and thumb caught imder the hyoid bone. Two cases of aortic aneurism were observed by the writer which were mistaken for asthma, owing to ab- sence of tumor, pulsation, thrill and bruit. The diagnosis was made by inspection and confirmed by ront- genograms. S. Solis Cohen (Inter- state Med. Jour., Jan., 1912). Inanition may follow in the rare in- stances in which the thoracic duct is compressed. In thoracic aneurism the distal vessels show a retarded and re- duced pulsation, so that the pulse may be weak or even absent from one wrist. In examining for aneurism of the aorta, one should carefully percuss the area of dullness of the great ves- sels, note the conduction of the heart sounds in this area, examine both radial pulses simultaneously, examine for the tracheal tug, note all evi- dences obtained by inspection or pal- pation, note carefully all the ana- tomical relations of the aorta, and ever keep in mind the possibility of aneurism. Arnold (Amer. Jour. Med. Sci., Apr., 1908). In cases of thoracic aneurism, de- lay or increased retardation of one of the radial pulses does occur. The same delay may or may not be pres- ent in the case of the corresponding carotid pulse. If the idea, based on experimental physics, be correct, that delay of the pulse-wave is only pro- duced as the result of the wave pass- ing through the aneurism, then the phenomenon of delay should be of most important diagnostic aid in the localization of the aneurism. Digital examination is not a reliable test of the presence or absence of delay. The finger may miss the delay when present, and may diagnose it when absent. A more delicate instrument, such as the clinical polygraph, is necessary. Leonard Findlay (Prac- titioner, Dec, 1909). In 2 cases observed by the writer, the arteriovenous aneurism became transformed into an arterial form, and this retrogressed spontaneously and totally in 1 case, partially in the other. Chevrier (Presse med., Dec. 19, 1918). Rupture is signalized by pain of sud- den onset with shock. Two cases of aneurism of the ab- dominal aorta apparently of arterio- sclerotic origin which ruptured into the duodenum. Marlow and Doubler (American Journal Med. Sci., April, 1918). Series of cases illustrating the many directions which aortic aneu- risms may take in relation to other organs. In 1 case the perforation was external, through the sternum; in 1 it was into the superior vena cava; in 1 it was into the left pleural cavity by waj' of the diaphragm; in 1 it was retroperitoneal; in 1 it was into the left pleural cavity by way of the left lung; in 2 it was into the left main bronchus; in 1 it was into the left ventricle; and in 1 it was into the pulmonarj- artery; 6 were therefore aneurisms which sprang from the arch of the aorta. Two were developed from thf abdominal aorta. Woolley (Amer. Jour, of S\-philis, Apr., 1917). As a result, the hemorrhage may escape externally through the skin, into the trachea, or into the alimentary ANEURISM (BABCOCK). 659 canal ; if into the pericardium there are evidences of acute heart compression ; if into the cavity of the thorax, of hematothorax ; if into the muscular substance, the formation of a progress- ively enlarging tumor. The rupture may be immediately fatal, or the pa- tient may live for hours or for days, and repeated or continuous leakage may occur. Rarely does recovery follow after an aneurism of one of the great vessels of the trunk has ruptured, al- though the patient may survive for days or weeks. Case of abdominal aortic aneurism in a man aged 41 years in whom the writer observed several hyperesthetic cutaneous zones, as described by Head. Such zones are segmental regions of the body corresponding to the various viscera, exactly at the sensory inner- vation of the skin, as described by Sherrington, Starr, Kocher, and Thor- burn. Trophic disturbances occur in the skin in disease of the arteries, as, for example, in zoster. The points noted in the study of the present case in- cluded the belt-like distribution of the radiations of pain due to the abdominal aneurism, these pains dating many years before the development of the symp- toms. E. Cedrangolo (Riforma medica, Mar. 23, 1907). COURSE. — Aneurisms tend to pro- gressively dilate and finally to rup- ture. In rare instances an aneurismal sac may remain stationary for many years, finally to again progressively dilate. In a third class spontaneous cure occurs by the coagulation of blood within the sac, which may completely consolidate it, with or without oblitera- tion of the arterial lumen. Any con- dition which interrupts or retards the circulation through the sac may favor this spontaneous cure. This termina- tion at times is followed by a fatal gangrene from obstruction of the col- lateral circulation. Plastic arteritis with thrombosis and obliteration of the artery may also lead to a cure. More frequently the aneu- rism progresses to rupture. The rup- ture may occur through the skin, mu- cous membrane, into a serous or syno- vial cavity or into the subcutaneous tissues, muscles, or fascial planes. There may be repeated moderate hemorrhages, one or several large hem- orrhages, or a rapid hemorrhage suffi- cient to cause almost instant death or a progressively increasing hemor- rhagic edema from a leaking aneurism. This may lead to gangrene. Suppuration of an aneurism occurs most frequently in the axillary region and usually results from the formation of an abscess adjacent to the sac. The sloughing of the sac wall may be fol- lowed by great hemorrhage as the ab- scess opens. Rarely does a plastic arteritis produce clotting and sponta- neous cure. DIFFERENTIAL DIAGNOSIS. — The expansile pulsation, bruit, and retardation of the distal pulse are fairly characteristic symptoms of aneurism. In a consolidated aneu- rism, or one in which the sac has been filled by clot, these signs may disap- pear. The history and presence of a firm mass in the wall of the blood-vessel are suggestive. Tumors and abscesses ly- ing upon large arteries may pulsate, but the expansile type of pulsation is absent. When the skin over an aneurism has become inflamed the condition may closely simulate an abscess, so that only by a careful study of the patient is a correct diagnosis finally to be made. Before the consolidation, compression of the main artery proximal to the aneurism may produce a characteristic 660 ANEURISM (BABCOCK). collapse of the sac, a cessation of pul- sation, and bruit, changes which cannot he produced in vascular sarcomas and other tumors which may simulate aneu- risms. In aneurisms of the thorax X-ray examinations are often diagnostic. In suspected aneurisms of the ab- dominal aorta loss or retardation of the femoral pulse should be especially looked for. The marked pulsation of the undilated aorta in tliin persons should not be mistaken for aneurism. In determining the compressibility of the aneurismal sac the greatest gen- tleness must be emj^loyed. We have observed hemiplegia to promptly follow the examination and the palpation of a carotid aneurism for the dislodgment of particles of contained clot. TREATMENT.— Dietetic, hygi- enic, and medicinal measures have been used since antiquity with the ob- ject of slowing the circulation and so simulating coagulation that a clot would fill the sac. The ancient method of Valsalva included absolute physical and mental rest, a \ery limited diet, with the deprivation of fluid, and re- peated venesections continued until the patient was too weak to lift a hand. The more recent method of Tuff- nell's was less severe, although rigor- ous; it consisted of a reduction in the diet and absolute rest in a horizontal position; 2 ounces of bread and butter are given for breakfast with 2 ounces of milk ; 3 ounces of bread and butter with 4 ounces of water or claret for dinner ; 2 ounces of bread and butter with 2 ounces of tea for supper. A fat diet has been advised by Powell, and the use of meats has been condemned. Cure by what was practically the Tufnell treatment. It consisted of as nearly absolute rest as possible, re- stricted diet for a week anrl later an ordinary fish diet, no stimulation, and potassium iodide, 10 grains three times a day. The dose was quickly and steadily increased so that by the end of the third week 60 grains were being taken three times a day, with no ill effects at any time. As a local application to the swelling, collodion was painted all over the surface every night and morning. Instead of continuing his previous downward progress, he commenced to improve from almost the commencement of the treatment, and was discharged apparently cured in six weeks. Young (Lancet, Sept. 22, 1906). Drugs are employed to reduce the cardiac frequency, to diminish arte- rial tension, and increase the coagula- bility of the blood. Potassium iodide has been considered to be the most valuable drug. Ten grains three times a day may be increased until 40, 60, or 200 grains three times daily are administered, according to the degree of tolerance. It is especially valuable in syphilitic patients. In aneurism of the aorta the writer urges antisyphilitic treatment, be- cause syphilis is the fundamental dis- ease in the majority of cases. Tiie best routine procedure is an intra- venous injection of 0.2 Gm. (3 grains) salvarsan every week until three doses have been given; then, if indi- cated, it may be repeated in 0.6-Gm. (10 grain) doses a month or 2 apart. In the interim intramuscular injec- tions of mercury about twice a week should he given in conjunction with potassium iodide, as this treatment often is efficacious and is followed by marked improvement. Selian Neuhof (Amer. Jour. Med. Sci., May. 1916). To increase the coagulability of the blood in the treatment of saccular aneurism? the subcutaneous injec- tions of gelatin were first recom- mended by Lancereaux and Paulesco. ANEURISM (BABCOCK'). 661 One or 2 Gm. of purest gelatin are dissolved in 100 c.c. of decinormal salt solution, and sterilized by heating to the boiling point for one-half hour on five successive days. Before use the gelatin is warmed to the temperature of the body and 100 c.c. injected under the abdominal skin every two, three, or four days. Plea for the use of injections of gelatin in aneurisni of the aorta. The danger of tetanus is removed if the gelatin is properly sterilized and no disagreeable effects are noticed by the patients. Lancereaux (Revue de therap., No. 13, 1906). Case of large traumatic aneurism occupying the lower half of the left popliteal space, and extending down- ward to a line about 6 inches below the knee-joint. After a prolonged and careful treatment by rest and flexion of the leg, which proved un- successful, the author tried repeated subcutaneous injections of sterilized gelatin serum. Seven injections were made, the intervals varying from seven to twenty days. The last injec- tion was followed after an jnterval of about ten days by complete cure. Le Dentu (Bull, et mem. de la see. de chir. de Paris, No. 10, 1905). Treatment of 40 cases showed that potassium iodide does not reduce the blood-pressure, although it often re- lieves pain. This can also be ob- tained by other means, notably by the injection of sterilized solution of gelatin. Gelatin does not reduce the blood-pressure, but in Rankin's and personal cases there was very marked relief of pain in almost every in- stance where such sj^mptom was a prominent feature. Mackinnon (Brit. Med. Jour., Oct. 4, 1913). Case of aneurism of the ascending portion of the aorta, with distressing symptoms, in which, after intraven- ous injections of mercury cyanide and gelatin had proved useless, per- cussion of the spine of the seventh cervical vertebra according to Ab- rams's method (see page 667) was tried, with signal success. The per- cussion was practised daily for five minutes. After eight sittings the pa- tient was able to walk five miles without distress, and resumed his work as a baker. R. Houlie (Bull, et mem. de la Soc. de Med. de Paris, May 8, 1914). In a certain percentage of cases, according to the writer, it may be possible to overcome the effects of an aneurism and induce a clinical cure by the treatment consisting chiefly in strict bed rest, reduction of the diet to 4 small meals a day without fluids; onl}' 300 c.c. of fluids *are permitted in the 24 hours. Venesection may be necessary and ice to the region of the aneurism, with local injections of ergot around the aneurism and injec- tion of gelatin into the buttocks, with potassium iodide internally. Mara- gliano (Gaz. degli ospedali, Jan. 31, 1915). A medical cure of an aneurism in the middle portion of the right supra- clavicular region was obtained by the writer. The man was kept abso- lutely quiet in bed. on a milk-vege- table diet, without much liquid, and he was given once a week for 20 weeks, a subcutaneous injection in the flank of 60 or 40 c.c. (2 or 1% ounces) of a 2 per cent, solution of gelatinized serum. As the Wasser- mann reaction was positive, mer- curial treatment was given at the same time. Improvement was rapid and pronounced. The aneurism sub- sided to a clinical cure. T. Castel- lano (Prensa Medica, Feb. 10, 1918). Several cures have been reported from the use of gelatin, but in other instances undesirable thrombi have formed in the larger veins, while teta- nus has followed the use of imperfectly sterilized gelatin. Should the clot which forms in the aneurismal sac soften and be absorbed, the gelatin in- jections may be repeated with a possi- bility of good efifect. The internal administration of cal- cium chloride and the subcutaneous 662 ANEURISM (BABCOCK). injection of horse serum have also been used to increase the coagulabihty of the blood. Case of aortic aneurism in which all the symptoms, except a slight headache, had disappeared as a result of the ad- ministration of calcium chloride for about two months. The calcium chlo- ride was given three times daily. The aneurism was clearly visible under the X-ray. Ambrose (Jour. Amer. Med. Assoc, Oct. 31, 1908). Arterial Compression. — The object of this method is to so slow the blood- current within the sac that a coagulinn may form. The pressure may be prox- imal to the aneurism and be carried out by means of a pad, tourniquet, or the pressure of the thumbs of assistants acting in relay. The pressure of the thumb is reinforced by a 6-pound weight, and before the thumb of one assistant is removed that of another is properly placed. Each assistant serves for fifteen or twenty minutes, and the treatment is continued for from, twenty- four to seventy-two hours. The method by compression is painful and when in- strumental may cause sloughing or gangrene. The digital compression re- quires many assistants and is trouble- some, but not so apt to cause sloughing. The compression occasionally cures, but often if the clot is deposited it is dissipated before organization has oc- curred. Three cases of aneurism followed, 2 for eight years and 1 for four years, in 2 of which permanent cure has re- sulted from treatment based on a reduction of vascular tension below the normal. The treatment consists in keeping the patient at rest in bed and in prescribing a diet from which soups containing an excess of fat; meats, es- pecially those cooked rare; game, fish, cheese, salted foods, tea, coffee, spirits, heavy beers, and an excess of wine are eliminated. Tobacco is also for- bidden. Drugs, such as nitroglycerin and sodium nitrite, were administered. The iodides have been overrated in this connection. Jn syphilitic aneu- risms mercurial injections are dan- gerous on account of their liability to affect the kidneys, and, as a conse- quence, to cause increased arterial ten- sion. The milk diet in connection with theobromine, which assists in eliminating vasoconstrictor poisons, is very helpful in reducing vascular tension. H. Huchard (Jour, des praticiens, Nu. 20, p. 307, 1906). Forced flexion ui the elbow and knee, the part being held by a bandage with the pad at the flexure, has been employed for small aneurisms of the extremities. The position is uncom- fortable and the method of little ad- vantage over other methods of com- pression. The isolation of a mass of blood within the aneurismal sac by the ap- plication of an Esmarch bandage be- low and above the aneurismal sac, while efficient in causing clotting, has led to gangrene of the extremity, and the method has been abandoned. It has been advised that an Esmarch l)andage be applied for one and one- half hours and then removed, with con- tinuous liglit compression of the artery above the aneurism for several days. Apart froiTi the danger of compression, another danger of these methods is in the completeness of the coagulation, which may extend into the collateral vessels and so destroy their function that gangrene follows. Arterial Ligature.— Eigature of the main artery just above the sac is espe- cially efficient in interrupting the circu- lation. This is Anel's operation, but was modified by John Hunter, who placed the ligature at a distance above the sac. where he supposed that the arterial walls were healthier. Anel's operation is now preferred to Hunter's. ANEURISM (BABCOCK). 663 The most important part of the ne\V surgical work with blood-ves- sels, especially with aneurism, de- pends upon the similarity of the se- rous coat of blood-vessels to the peritoneum. Like the latter, the former throw out lymph for pur- poses of repair. Irritated surfaces in apposition adhere. Torsion of blood-vessels also causes quick plas- tic occlusion so that arteries of the third class may be thus treated in place of by ligation. Aneurism treated by digital pressure, by the introduction of coils of wire, or by electric needles causes exudation of lymph from the serous coats, followed by adhesion of apposed surfaces. The new work in suturing blood-vessels depends for its safety upon the prompt plastic repair of the serous coats. Morris (Annals of Surg., July, 1908). According to the writer, it has been found by English surgeons, contrary to the commonly accepted ideas, that in many cases simultane- ous ligation of vein and artery may be safer as regards both life and avoidance of gangrene than ligation of the artery alone. H. S. Valentine (Trans. Mo. State Med. Assoc; Jour. Amer. Aled. Assoc, May 1, 1920). When on account of anatomical con- ditions the ligature cannot be placed above the sac the method of distal li- gation, such as Basedow's, in which the main vessel is ligatured, or War- drop's, in which one or more of the chief branches is secured as by ligation of the right subclavian for aneurism of the innominate artery, may be tried. Rarely are they efficient. A successful case (the ninth with recovery) of ligation of the innom- inate artery. The patient was a colored man aged 27 suffering from subclavian aneurism; the innominate only was tied with a largest-sized braided silk ligature in a "granny" knot drawn just tightly enough to approximate the vessel walls, but not to crush its coats. The ligature came away 51 days after the opera- tion while the wound was being dressed; the recovery was good prac- tically in 20 days. Burns (Jour. Amer. Med. Assoc, Nov. 14, 1908). In aneurisms at the root of the thigh the writer resorts to prelimin- ary elastic compression with the Esmarch band or by Momburg's method. The blood flow can always be arrested beforehand by passing a strand of catgut beneath the vessels and having an assistant exert mod- erate upward traction on it. In none of his cases, whether of spontaneous or traumatic aneurism, did gangrene follow quadruple ligation of the fem- oral artery and vein above and below the aneurism, with extirpation of the latter. Even in a large pathological aneurism, with removal of 17 centi- meters of the external iliac arterj- and of the femoral trunk, superficial as well as deep, not the least circu- latory difficulty followed — probably in this case because the aneurism was of about 10 years' standing. Much delay in operating on aneurisms, es- pecially in war practice, is inadvisable, for as time passes the aneurism ex- tends, and increasingly firm adhesions with the collateral veins, nerves, and neighboring organs or tissues become established, rendering dissection dif- ficult. Potherat (Presse med., June 21, 1917). The late war afforded much ex- perience with traumatic aneurisms. The practical conclusion from dis- cussions and statistics, as expressed ,by the writers, is that ligation and resection of the aneurism constitute the safest and best treatment in the majority of cases. Only under exceptionally favorable conditions should end-to-end suture be con- sidered, though this is sometimes the only means to save the limbs. Len- ger, Strassen and Vonsken (Arch. Med. Beiges, Aug., 1920). Dix's Operation. — The artery is ex- posed and encircled by a strand of silver wire. The ends of the wire are brought through the tissues to one side of the wound, and are twisted over a 664 ANEURISM (BABCOCK). split cork until pulsation ceases in the aneurism. Later slight pulsation re- turns to the sac, and after two or three (lays the wire is tightened hy placing wedges under the loop. Ahout the fifth or sixth day the wire is cut and re- moved. Excision of the Sac and Implanta- tion.— The interposition of a segment of an adjacent vein has also been tried, but the procedure has rarely been suc- cessful. Removal or Obliteration of the Sac. — The ancient method of Antyllus, in which the sac was dissected out or opened and packed, has been suc- ceeded by the modern obliterative method of Matas. In this operation the patient is anesthetized, a tourniquet applied, the sac is opened by a longi- tudinal incision, emptied, and the mouth of each vessel is exposed within the sac and sutured from the inside by separate silk or chromicized catgut sutures. The redundant walls of the sac are then so enfolded and sutured as to form a solid pad under the skin. The advantage of this method lies in the fact that the sac is not loosened from the adjacent tissues, and, therefore, there is little risk of injuring adjacent col- lateral nerves and veins. Matas's method combines the ad- vantages of ligation and excision, while at the same time it is easier, safer, and may be more conservative. It is suitable both in the fusiform and sacculated types of the disease. After applying a constrictor above the site of the disease, if in a limb, or temporarily ligating the proximal and distal trunks, if the carotid is the vessel at fault, the operator cuts into the sac, thoroughly removes the contained clots, rubs the serosa with gauze, and proceeds to in- sert sutures. The sutures, preferably catgut, are first applied to the openings of all vessels entering or leaving the sac; then the deeper portions of the sac are closed by two rows of contin- uous Lembcrt sutures. The elastic con- strictor is now removed, and if any blood escapes one or two points of suture are inserted to control this. The next step consists in folding the excess of sac wall on itself, and in so doing inverting the edges of the skin wound. The operation thus performed has been very successful, and in some cases of sacculated aneurism the circulation may be re-established through the repaired vessel. Binnic (Jour. Amer. Med. Assoc, June 25, 1904). Results of endoemeurismorrhaphy (the writer's method) in 85 operations by 52 surgeons up to the present date. The legitimate mortality of the operation itself was 2.i per cent.; of secondary hemorrhage, 2.3 per cent.; of gangrene, 4.6 per cent. Eliminat- ing 3 of the gangrene cases in which there was simultaneous injurj'^ and ligation of veins or secondary ligature of an artery, the percentage of this accident is 1.1 only. The total of post- operative deaths from all causes was 7 to 78 recoveries. The percentage of relapses, which occurred only in the reconstructive operations (4 in 13, or 28 per cent.), was only 4.7 per cent, to the total. The author be- lieves that the fundamental principle on which the operation is based, viz., that the endothelial lining of the vas- cular system which is continued in the aneurismal sac is analogous in its pathological behaviour to the reac- tions and reparative processes which occur in the endothelial surfaces of the other serosa, such as the peri- toneum and the pleura, has been ab- solutely confirmed by the experience in these 85 cases. They have also dis- proved Scarpe's law that complete obliteration of the vessel is an essen- tial to the cure, which result is also supported by the facts of the suture and repair of arteries. An important point of the technique is the prophy- lactic hemostasis, which must be made absolute, and the problem in- creases in complexity and difficulty the higher the operation, and the writer mentions the method and ap- ANEURISM (BABCOCK). 665 pliances for this purpose. Experi- ence demonstrates that in all sacci- form aneurisms with a single orifice of communication the closure of this orifice by suture without interfering with the lumen or the capacity of the vessel is to be looked on as ob- ligatorj% The indication for the re- constructive operation, however, is fusiform aneurism with separate ori- fices of entrance and exit. In the vast majority of cases of aneurism of the extremities the simple oblitcra- tive procedure proved satisfactory. It gives a cure with less risk to distal parts than ligature or extirpation. In- dications in any given case will not be entirely satisfactory until we have a sure clinical proof of the adequacy of the collateral circulation. Korot- kow's method of testing the most peripheral blood-pressure may be the proper solution. R. Matas (Jour. Amer. Med. Assoc, Nov. 14, 1908). The advantages of Matas's endo- aneurismorrhaphy are as follows: It is more radical in its effects than liga- ture and extirpation; it is free from risk of injurj-; it is only exceptionally followed by gangrene; it does not in- terfere with the collateral circulation; it prevents any danger of injury of a vein, and is applicable to cases in which extirpation is no longer pos- sible. For suture chromicized catgut or fine silk is employed. The method is chiefly indicated in cases in which provisional hemostasis can be carried out and where the aneurismal sac is accessible. Altogether 149 cases have been reported, in 131 of which the lower extremity was affected. Among the last 64 cases there have been no deaths, no recurrences or secondary bleeding, and only one instance of gangrene. Gardner (Gaz. d. Hop., No. 118, 1910). A second method is Matas's con- servative endoaneurismorrhaphy, to be used for sacculated aneurisms open- ing- by a narrow mouth into the main vessel. This opening- is sutured from the inside of the sac and the wound reinforced, pleating and suturing the overlying sac. In reconstructive endo- aneurismorrhaphy an attempt is made to restore the normal luinen of the artery in a fusiform aneurism. A rub- ber tube may be temporarily intro- duced as a guide between the afl'erent and efferent mouth of the sac, and the walls of the sac so sutured as to re- store a canal having the lumen similar to that of the adjacent artery. This line of suture is likewise to be rein- forced by pleating and suturing the redundant walls of the sac. Report of a case of reconstructive aneurismorrhaphy in the third part of the axillarj- artery, the aneurism having been the result of a gunshot wound received 2 years previously. The aneurism and a portion of the axillary artery both above and below were dissected free and Crile artery clamps applied above and below the tumor. The aneurismal sac was then defined up to its point of origin from the artery and opened by a longi- tudinal incision. At the junction of vessel and sac was a ring of almost cartilaginous density. The sac was cut away so that only a thin rim around the neck was left. With a non-cutting fine needle a continuous suture was introduced, beginning above and finishing below the open- ing and passing through the arterial wall immediately adjoining the thick ring. Mattress sutures of fine silk were used. A second stronger silk suture was then introduced, the needle traversing the artery wall on either side and returning similarly through the rim of the sac, thus em- bracing the hard ring and securing apposition of its opposite side. Re- moval of the clamps revealed no ooz- ing. A fascia lata graft was fixed as a collar about the vessel to diminish the strain on the suture line. Three months later there was no sign of j'ielding and the brachial pulses were equal. C. J. Marshall (Brit. Med. Jour., i, 379, 1921). 666 ANEURISM (BABCOCK). Temporary partial obliteration of the main artery by use of metallic rings or clips; Halstead and others have devised rings or clips composed of aluminum or other metal which may be applied to an arterial trunk in such a manner that the lumen in the vessel is reduced or obliterated. By reducing; the lumen the current in the artery and sac distal to the ring may be so slowed as to favor curative coagulation, and if properly applied it has been found that these rings are well tolerated by the arterial wall, and have not the same tendency to ulcerate into the lumen of the vessel as a ligature. The application of a ligature is not feasible in the case of the aorta, for in every case in which a ligature has been employed the patient has died, if not from the immediate danger from the operation, then some days or weeks later from secondary hemorrhage due to the ligature cutting its way through the wall of the artery. Macewen's Acupuncture. — This method aims to scarify the lining of the sac so that the granulations form upon which the blood may coagulate. One or more long fine-silk needles are thrust into the aneurism so that their points just touch the opposite wall. The pulsatile movements of the sac wall cause the needle-points to scratch the lining of the sac. The needles are left in place some hours, their position then is so changed that as large an area as possible of the lining will be abraded. The method is of very limited value. Electrolysis increases the efficiency of Macewen's method. Insulated nee- dles are passed and a galvanic current from 20 to 30 milliamperes. Needles should be permitted to touch the oppo- site wall of the sac so as to produce the delicate abrasion as in acupuncture. Report of 2 cases of thoracic aneu- rism upon which the Moore-Corradi operation of wiring with electrolysis had been performed over 4 years pre- viously. In the first, 17 feet of No. 29 gold "clasp" wire had been used and in the second 22>4 feet. Active antisyphilitic treatment was insti- tuted in both patients with great benefit. The best result is obtained when the wire is so introduced as to bring it as much as possible in con- tact with the wall of the aneurism. This permits the clot produced by the electrolysis to come in contact with vitalized tissue from which it can become organized. W. C. Lusk ("Annals of Surg., Ixiv, 680. 1916). Moore's method consists in the use of a delicate wire so tempered as to coil within the sac, where it is permitted to remain permanently. A small, hol- low needle is introduced into the sac until the blood flows and from 5 to 20 feet of wire, according to the size of the sac, passed through the needle. The end of the wire is then pushed through the needle or cut close to the skin and made to imbed itself. The Moore-Corradi method con- sists in passing the current from 20 to 80 milliamperes through the coil of wire which has been introduced into the sac. A wire of fine drawn gold is preferred, and from 5 to 20 feet intro- duced, as in the Moore method. The current is permitted to flow about one hour, negative pole being connected with a pad upon the patient's abdomen or back. The wire is permitted to re- main permanently within the sac. Aneurism of the left subclavian artery in which 20 feet of gold wire were introduced into the sac through a hollow needle, and a galvanic current, gradually increasing from 1 to 80 milli- amperes, was employed for about one hundred and ten minutes. The pulsa- tion and size of the tumor temporarily decreased and afterward increased, and ANEURISM (BABCOCK). 66; death occurred on the twentieth day after operation, due to exhaustion and pressure thrombosis. Daland (Penna. Med. Jour., Dec, 1903). Three further cases of sacculated aneurism of the aorta successfully treated by wiring and electrolysis. The second case was too advanced for anything more than palliation. One of the most important effects is the relief of pain. This is usually imme- diate. H. A. Hare (Jour. Amer. Med,* Assoc, Ixxvi, 587, 1921). These methods have chiefly been em- ployed for aneurisms of the thoracic aorta. Occasionally cures are reported, but failures are frequent and fatal acci- dents have occurred. It is obvious that even in so-called cures the patient's ultimate condition is not a normal one. Sterilized horsehair, silk, and catgut have also been tried, but with question- able benefit. A recent addition to the methods of treatment is that of Abrams, which, though qualified by him as palliative, seems to have produced lasting bene- ficial effects in a large number (40) of his cases. It consists of repeated con- cussions over the seventh cervical vertebra, which are thought by Abrams to cause, through the vaso- motor system, contraction of the diseased vascular area. Confirmatory evidence is still too scant to warrant any opinion as to the actual value of this method. A. Abrams, of San Francisco, claims that the subsidiary center of the vaso- constrictor nerves of the aorta is located in the spinal cord in proximity to the spinous process of the seventh cervical vertebra, and that by stimulation of the center in question by concussion the normal as well as the abnormal aorta may be brought to contraction. Ample evidence is furnished of the latter fact in his work on spondylotherapy. The method, in brief, which he suggests in the treatment of aortic aneurism con- sists in concussion of the spinous process of the seventh cervical verte- bra. He deprecates the employment of the conventional vibrating appa- ratus. The vibratory apparatus which the physician must employ is one giving the percussion stroke. All other motions, such as oscillations, shaking, and friction, interfere with results. In the absence of a suitable apparatus, a pleximeter (a strip of linoleum or thick rubber) and a hammer, to the end of which is fixed a piece of hard rubber, are employed. The pleximeter is applied to the seventh cervical spine and is struck a series of rapid and moderate blows by the hammer. The daily seances, according to results, may last from five to fifteen minutes, but during the seance the treatment must be interrupted from time to time to avoid irritations of the skin. The results of Abrams's method are usually immediate, great relief follow- ing a few seances. When the writer first encountered the monograph of the latter on the subject, he was rather skeptical, although Abrams anticipates such criticism in his book by observing that any merit attached to his method may be obscured by its simplicity. The writer presents the history of a personal case suflfering from aneurism of the thoracic aorta which was treated successfully by the "concussion method" of Abrams. The aneurism had per- forated the chest wall. Within one week all the symptoms had disappeared, and fourteen months after the patient's discharge he was as well as when dis- missed. L. St. John Hely (Amer. Jour, of Physiol. Therap., July, 1910). Case of aneurism of the thoracic aorta treated by Abrams's method. After the first daily seance of concus- sion, lasting ten minutes, the systolic murmur over the aorta almost disap- peared. Three days later the aneuris- mal dullness measured transversely 2.6 cm. After two more days the aneurism measured 2 cm. and the patient's weight was 123 pounds, an increase of 5 pounds. Two days later there was absolutely no dullness over the site of 668 ANEURISM (BABCOCK). the aneurism, the pains in the chest were gone, expectoration was re- duced about 50 per cent., but the cough continued with less frequency and severity. After about two months the patient's weight was 135 pounds. He had absolutely no symptom bej'ond an occasional slight cough. Turnbull (Med. Record, Sept. 9, 1911). Report of a case of aneurism of the thoracic aorta treated successfully by Abrams's method. There was no X-ray verification of the condition in this case, but the physical signs re- specting the aneurism and the re- sults of treatment were absolutely positive and unmistakable. Boyd (N. Y. Med. Jour., Oct. 21. 1911). ARTERIOVENOUS ANEU- RISM.— These conditions, termed by Hunter aneurism by anastomosis, are characterized by an arteriovenous fis- tula. They may be divided into two chief forms: — (a) Aneurismal varix is character- ized by the direct communication of the artery with the vein. Tlie blood-pres- sure is much higher in the artery ; the arterial flow is forced into the vein, which becomes thickened, dilated, sac- culated, and tortuous. The condition is usually due to the incised wound involv- ing the contiguous walls of an artery and vein, and gunshot wounds. Occa- sionally they result from contusions without external wound, and may even develop spontaneously. Tn the older days the common cause was phlebot- omy. In order of frequency the bra- chial, femoral, ])opliteal. carotid, tem- poral, subclavian, and axillary arteries are involved. Instances are recorded in which the condition has spontane- ously occurred in connection with the abdominal and thoracic aorta, and after gunshot wounds of the head a fistula may form between the cavernous sinus and internal carotid arterv. (b) Varicose Aneurism. — The vein comnumicates with the artery through the medium of an aneurismal sac. This usually develops from a traumatic aneu- rism which becomes adherent to an adjacent vein and finally opens into it. lioth the artery and the vein may be injured simultaneously and an interme- diate blood-clot first form, the sac "finally replacing ihe area occupied- by the blood-clot. Such an aneuristn may form at the ends of the divided vessels in an amputation stump. An arteriovenous aneurism with an arterial sac, such as that developed from the erosion of a true aneurism through the wall of an adjacent vein, is rare, and has been classified as a third variety of arteriovenous aneurism. Symptoms. — A marked pulsation which is communicated widely to the comnumicating veins is present and usually associated with a loud, whistling bruit. The bruit is both systolic and diastolic. The thrill may be palpable. The interference with the normal circu- lation in the vein may produce stagna- tion, local cyanosis, pigmentation, ec- zema, elephantiasis, muscular atrophy, ulceration, rarely gangrene. The pres- sure upon the nerves may result in paresthesia or paralysis. Among 42 cases of traumatic arte- riovenous aneurism observed by the writer in the Serbian army in 4 years, all operated on by him, 24 were of the direct type, artery and vein being in immediate i,ommunicaticn. The common carotid artery was involved in 3 instances; the subclavian in 1; the brachial, 2; external iliac, 3; fem- oral, 13; and popliteal, 2. Often no hematoma around the aflfected ves- sels was found. Symptoms generally began only a few days and sometimes 1 or 2 weeks after the injury, the most characteristic sign being an audible thrill originating at the point ANEURISM (BABCOCK). 669 of communication of the vessels and transmitted centrifugall}' along the artery and centripetally along the vein. At operation, especially in cases of external iliac or femoral in- volvement, a pronounced dilatation of the vein at and above the point of communication was noticed; like- wise, a narrowing of the arterial trunk below this point. Thus, a part of the blood brought l)y the artery, entering the vein, is transmitted by the latter, not in a peripheral, but in a central direction, toward the heart. The centripetal transmission of tlie thrill along the vein and the ab- sence of peripheral varicosities are thus accounted for in these cases of direct arteriovenous aneurism. Soub- botitch (Bull, de I'Acad. de med., May 30. 1916). Treatment. — The treatment of ar- teriovenous aneurism is usually op- erative, as the disease is usually per- sistent and progressive. The artery may be clamped above and below the opening and the opening in the artery and vein closed by arterial suture. Where a thoracic aneurism is present the sac may be split and the communi- cating opening sutured from within the sac. as in Matas's aneurismorrhaphy. In some cases it may be necessary to ligate the artery above and below the point of communication. As a rule, the vein should not be ligatured. In small traumatic aneurisms in which the distended inner coat of the vessel bulged through tlie external coats we have found it possible to re- duce the hernia-like protrusion and to reunite the median adventitia by tine silk sutures, which reinforce the union by suturing adjacent connec- tive tissue to the arterial wall. Analysis of 161 cases of arterio- venous aneurisms published since 1889. The femoral was involved in 80 and the popliteal in 35 cases. Much better results are obtainable, as a rule, from operating directly on the sac than from ligatjres. The main drawback to a complete cure is the frequent coexistence of nerv- ous lesions complicating the aneu- rism, which are generally solely re- sponsible for the postoperative dis- turbances. Only when direct action on the sac is impossible should liga- tures be given the preference. Re- moval of the sac offers the same ad- vantages over incision for the arte- riovenous as for the arterial aneu- risms. Monod and Vanverts ( Revue de chir., Oct.. 1910). In none of 15 cases of traumatic aneurism seen l)y the writer was he satisfied with simple ligature of the vessels, and the accompanying dan- ger of relapse. The injuries in all were too complex and extensive to make it possible to carry out lateral suture in order to preserve the per- meability of the arterial trunks. An essential condition for the perform- ance of extirpation of arteriovenous aneurisms is to have a wide opening on to the aneurism; thus, for aneu- risms in the axilla tlie pectoralis major was divided vertically; for aneurisms in the carotid region the sterno-mastoid was divided horizon- tally. These large divisions of mus- cle do not give rise to any serious functional trouble later if the divided ends are accurately sutured together at the end of the operation. Auvra)' (Bull, et mem. de la Soc. de Chir. de Paris, Apr. 20, 1915). In 102 operations for aneurism due to war injuries the best treatment was found liy the writer to be suture of the artery; it was performed in 74 cases; in most of the cases the suture was along the axis of the vessel; in only 3 cases was transverse suture performed. In arterial aneurism lat- eral suture was a simple operation. This was not the operation for arte- riovenous aneurism. In 36 cases the wounded piece of artery was resected and the ends sutured circularly. Transplantation of a piece of vein to fill in the gap was not found neces- sary. Circular suture was easily per- 670 ANGINA PECTORIS (VICKERY). formed, even on the larg^er arteries; intima was applied to intima and a continuous suture inserted. Small arteries were ligated. Where large veins ran through infected aneu- risms, they were ligated in 2 places and resected. Death occurred in 8 of his operated cases, 4 of the fatal cases being aneurisms of the sub- clavian. Bier (Beitr. z. klin. Chir., xcvi, 556, 1915). In 13 cases of gunshot aneurisms treated by suturing the injured ves- sels, recovery was prompt and com- plete in all, and there have been no complications since. This result was also obtained in 25 of 29 cases in which the vessel was ligated, in 2 amputation was required later, and 2 others died from hemorrhage from an erosion. The circulation pro- ceeds in all the cured cases with nothing to suggest that the men are not quite normal. von Ilaberer (Wiener klin. Woch., May 6, 1915). In traumatic aneurism the best op- eration is considered by the writer to be quadruple ligation. It may be applied even in cases where there is perforation of the carotid at the bi- furcation, when quintuple ligatures are applied; none of the cases so op- erated upon has been lost. Quenu (Bull, et mem. Soc. de chir. de Paris, xli, 592, 1915). To lessen the dangers of gangrene after operation for aneurism, the writer resorts to the following method: The limb is made anemic by inhibiting the entire circulation below the aneurism for 2 minutes by means of a constrictor, then releasing the constriction and compressing the artery above the aneurism. If an active hypercmic reaction is obtained the collateral circulation is sufficient. L. Moszkowicz (Beit. z. klin. Chir., xcvii, 569, 1915). Conditions related to aneurisms in- clude certain nevi, cavernous ang^i- oma, aneurism by anastomosis, and arterial angioma or cirsoid aneu- rism. These conditions suggest new growths or tumors more than aneu- risms. Some are congenital ; others are acquired, and the aneurism by anastomosis, a vascular tumor con- sisting of involved arteries, veins, and capillaries, which may reach an enor- mous size, is present. The arterial angioma or cirsoid aneurism usually occurs upon tlie liead about the time of adolescence. It may be congen- ital or follow traumatism. The ar- teries are enormously dilated and very tortuous ; the bruit may be so loud as to interfere with the patient's sleep. These conditions are usually treated by electrolysis, ligation, or excision. \V. Wayne Babcock, Philadelphia. ANGINA LUDOVICI. See Pharynx and Tonsils, Diseases of. ANGINA PECTORIS.— DEFI- NITION.— Angina pectoris (^steno- cardia, breast-pang) is the name given to a group of symptoms which usually depends upon organic disease of the heart or aorta. An attack consists in the sudden onset of agon- izing pain in the precordial or sternal regions, accompanied by a feeling of constriction and in severe cases by a sense of impending death. The pain radiates into the back, the shoulders, and the arms, particularly the left. The patient is pale, haggard, motion- less, and often bathed with cold per- spiration. SYMPTOMS.— Suddenly, after ex- ertion, excitement, or a hearty meal, the patient feels an excruciating, burning, or tearing pain in the heart or beneath the sternum, accompanied with a sense of constriction (anger e. to throttle), as if the heart were in a vise. The pain radiates into the back, upward into the shoulders, and ANGINA PECTORIS (VICKERY). 671 down the left arm, often even to the fingertips. It may be felt in both arms, in the neck and head, and even in the trunk and lower extremities. "In true angina the seat of the pain may be entirely away from the chest, and may be, as in Lord Clarendon's father, at the inner aspect of the arm, or about the wrist, or in rare in- stances confined to the side of the neck, or even to one testis" (Osier). After an attack, there may be tender- ness above and outside the left nipple and in the left arm. The pain is explained by James Mackenzie as a sensory reflex due to irritation of the 1st, 2d, and 3d dorsal and 8th cervical nerves, and the sense of constriction to reflex stimulation of the intercostal ner\'es. Paroxysms occur in which pain is slight or absent (angina sine dolore). Early attacks are often of this sort. Later on there may still be no pain, or the paroxysms may sometimes be painful and at other times not. A feeling of numbness accompanies the pain. There is a sense of impend- ing dissolution. The sufferer sits or stands immobile and hardly dares to breathe. Yet there is no real dyspnea. The face is pale or livid; the forehead wet with perspiration. The pulse may remain strong and regular. Usually it is accelerated and of in- creased tension. A pulse of habitual high tension may be somewhat lowered during the attack (Macken- zie). The pulse may intermit or vary. Exceptionally it is slowed. The paroxysm lasts a few seconds or minutes, — sometimes half an hour or even several hours. At the end of it the patient often belches gas or vomits or has a movement of the bowels, with great relief. The in- ference that indigestion has caused the paroxysm is natural, but probably erroneous ; although it is true that even slight exertion directly after a meal may precipitate an attack. The less found wrong with the heart upon examination, the more certain may one be of the diagnosis. In a series of 500 cardiovascular and cardiorenal cases there were 35 cases of genuine angina pectoris. One- third had succumbed to an acute an- ginal attack, and two-thirds to grad- ual cardiac death. J. E. Talley (Med. Rec, Nov. 6, 1915). The cases may be divided into two groups: the angina of effort and the angina of decubitus, but in the later stages of either form of the disease the distinction becomes less clearly marked, and either form may rapidly be followed by the other. In deter- mining what organic lesions may be present, very great importance is at- tached to the results of radioscopic examination. As a rule, in the angina of efifort, aortitis is present. The qualitative changes shown by radios- copy are diminution of transparency of the walls of the aorta, which on the screen look either uniformly dark or sown with scattered dark patches. Very often there is more or less com- plete immobility of the vascular con- tours, indicating loss of elasticity in the vessel walls. Radioscopy may also reveal modifications in volume whose detection has escape.d ordinary methods of observation. One change' of much significance in the diagnosis of the epigastralgic form of the dis- ease is enlargement of the aortic arch. H. Vaquez (Arch, des mal. du coeur, Mar.-Apr., 1915). The attack may prove immediately fatal. If not, the patient is left ex- hausted, but regains his usual condi- tion in a few hours or days. The attack is almost sure to be re- peated. This may happen in an hour or not for weeks or months. The length of the interval depends greatly 672 ANGINA PECTORIS (VICKERY). upon the persistence of the patient in avoiding the exciting causes. After a severe attack, rest in bed is desir- able for several days, or, if the patient is much enfeebled, for a week or two. Successive paroxysms occur with gradually increasing readiness. The diagnosis of angina pectoris, at least in its milder form, cannot be made from the history alone. The other forms of cardiac pain, of toxic or neurotic origin, the latter espe- cially in women, may exactly simu- late a true angina pectoris. In diagnosing between true and false, organic or functional, there is one physical sign which the writer believes positive. It is so slight, and apparently so insignificant, that one almost hesitates to mention it. It is simply a slight clicking sound, of a harsh or rough quality, accompany- ing, or following at barely percept- ible interval, the sound of aortic closure. It is not an accentuation of the closure sound of the valve, such as the loud, clean, "cork and bottle" aortic second sound, which is sig- nificant of high arterial tension. G. R. Butler (Archives of Diagnosis, Oct., 1909). The most frequent exciting cause of seizures is overexertion, though walking, eating heartily, and emo- tional outbursts have also their etio- logical place. A sense of constric- tion without pain occurring after the ordinarily exciting causes is alwaj's highly suggestive. A striking fact is the frequency witli which patients remain unwarned by experience of the dangers of carelessness. A large proportion of patients with embolic or thrombotic obstruction of a large branch of a coronary artery have died suddenly soon after the accident, and yet at autopsy pathologists have found evidence of long-standing ob- struction. Coronary obstruction may cause an anginal seizure, and yet the patient not die at once nor even soon. J. B. Herrick and F. R. Nuzum (Tr.ans. Amer. Med. Assoc; N. Y. Med. Jour., June 16, 1917). While the physical pain of angina pectoris is the essential and initial manifestation of the syndrome, the angor, an expression of tiie high de- gree of emotional anxiety, is a close second, in certain particularly emo- tional subjects, the fright awakened by a slight attack of pain is so marked that the primary, essential manifestation may be overlooked by the examining physician. The fear of death in angina pectoris seems to re- sult from the combined influence of the physical pain and the intense sub- jective exhaustion, which leads to the mental conception that, as some patients have expressed it, all the processes and activities of nature have ceased. R. Benon (Presse med., Jan. 21, 1920). DIAGNOSIS. — In true angina pec- toris skilled observers almost invaria- bl}- lind evidence of organic cardiac or aortic lesion. In a supposed case these should be sought most care- fully. Particularly to be looked for are arteriosclerosis, hypertrophy or dilatation of the left ventricle, aortic regurgitation, and feebleness of the muscular power of the heart with facial pallor, sometimes lividity, sweats, and coldness of the surface. According to Mackenzie, angina pec- toris is an evidence of an exhaustion of the function of contractility, the pain and reflex muscular contraction being refle.x phenomena due solely to an impairment of the contractile function of the heart. This does not, however, explain the en- lire situation, for W. j. Pulley (N. Y. Med. Jour., Nov. 8, 1913) believes there must of necessity be present with it a great distress of the function of tonicity, if not a beginning impairment. The pains are protective, by causing the patient to cease muscular efforts, and tend to rest ihe heart. The fear also is protective by causing the patient temporarily to cease worries and excesses of all kinds. The flushed face, due to reflex stimulation of the vasodilators of the superficial capil- laries, also tends to reduce vascular super- ANGINA PECTORIS (VICKERY). 673 tension. The contraction of the intercos- tal muscles is also protective; it prevents deep breathing, which increases the arte- rial tension, and provides a splint to pro- tect the already stretched and weakened aortic walls. Editors. Intercostal neuralgia causes pain along- an intercostal nerve, not radiat- ing- as in angina pectoris. It presents points tender to pressure near the vertebrae and sternum and in the axilla. It is not associated with dis- ordered circulation. It is more com- mon in women than in men. Gastralgia is apt to occur when the stomach is empty. The pain does not stream into the shoulder and arm. While there may be collapse and a sense of impending death, there is no evidence of heart disease. Like in- tercostal neuralgia it is likely to occur in anemic young women, rather than in middle-aged men. On the other hand, the pain of true angina pectoris may be felt lower down than the precordia. And, as already stated, the termination of an attack may be marked by the dis- charge of gas. Particularly if there is no extreme cardiac pain, this may lead the patient, and in some instances has led his physician astray. Cardiac asthma is dyspnea due to a weak heart and occurring more or less paroxysmally. Pain is not prominent. The picture is apt to in- clude pulmonary edema, enlarged liver, and dropsy, and it could hardly be mistaken for angina pectoris. Mitral disease is not apt to be asso- ciated with angina pectoris, and relief from attacks is often experienced when a mitral leak develops in an -aortic case. The recognition of cardiac lesions observed after attacks of angina pec- toris is of great importance, inasmuch 1-43 as it leads the physician in charge to insist on perfect rest for the patient for days or even weeks after a severe attack, and thus prevents, in some in- stances, sudden death. The cases in which the attacks are followed by the appearance of clinical signs in the heart may be divided into three classes. In the first group there is a rise of temperature and a slight en- largement of the cardiac area of dull- ness. The fever may be slight, but if other causes are excluded it is of great value in the diagnosis of myo- carditis following angina pectoris. In the second group there is, in addition to fever, a distinct dilatation of one or other of the cardiac cavities, which can readily be discerned on physical exami- nation. Finally, in the third group, there develops an acute endocarditis following an attack. In spite of the fact that clinically the occurrence of acute endocarditis after angina pectoris is not a well-recognized phenomenon as yet, it has long since been described patho- logically. Kernig (Roussky Vratch, Oct. 30, 1904). "Pseudoangina." — Pseudoangina pectoris, or hysterical angina, occurs in females or neurasthenic men, usually under the age of 40, without evidence of organic cardiovascular changes. There are low tension, feeble second sound, and soft arteries. The attacks are spontaneous and are apt to be nocturnal and periodic (menstrual). They last an hour or two, being more prolonged than the true paroxysms. The patient is agi- tated, writhes, or walks about the room, and talks. The heart feels not constricted, but distended. The pain is not apt to be so severe as in true angina pectoris. Paresthesise and vasomotor symptoms are prominent. The patient's symptoms are some- times colored by his having consulted encyclopedias and the like (Broad- bent). Death never occurs. . 674 ANGINA PECTORIS (VICKERY). Angina pectoris in its typical form is a rare disease. Pseiuloangina, or car- diac asthenia, as it is frequently called, is much more common. It is erroneous to speak of angina pectoris as a neuro- sis of the heart, as in the great majority of instances there arc organic changes in the coronary circulation, the cardiac muscle, or lesions of the aortic orifice. Neurotic angina is exceptional, is al- most always associated with spasm, or with a sudden increase in intracardiac pressure. Beverly Robinson (Amer. Jour. Med. Sci., Feb., 1902). Painless angina is much more com- mon than one would suppose it to be from the infrequency with which it is mentioned ; but, in aM probability, the disease is not always recognized, and the patient's sufferings are attributed to hys- teria or some reflex disturbance. When the symptoms are accompanied by a di- lated right heart or distinctly athero- matous changes the diagnosis is easy, but when physical signs are absent it is difficult to arrive at an absolute opin- ion. I f, when free from the paro.xysms, the patient continually suffers from a feeling of weight or distress over the prccordia, and has a tendency to take occasional deep inspirations, there is a strong probability that the right ven- tricle is affected, and this amounts to certainty if the symptoms are invariably produced or aggravated by exertion. This form of angina is entirely different from the painful variety, and in many instances demands a diametrically oppo- site treatment. W. W. Kerr (Jour. Amer. Med. Assoc, May 29, 1909). Hysteria. — It should, of course, be remembered that hysteria may be combined with organic disease, and that a careful physical examination should be made in any suspected case; but the discover}- of mitral dis- ease would not be inconsistent with a diagnosis of pseudoangina. There is a nervous form of syphilitic angina which is distinct from hysterical angina pectoris. The two conditions may be distinguished as follows : In hysterical angina the attacks come on. as a rule, at night; on examination there are found hysterical areas on the skin of the chest, and the attacks begin with paresthesia of such an area, and end in tears, sobs, and other manifestations of excitement. The syphilitic attack of the nervous type is preceded by fatigue, not by ex- citement. It is very important to distingish the nervous sj'philitic type from the organic syphilitic angina, which depends upon a lesion of the heart muscle itself. The chief char- acteristic of these is the presence of periodic attacks of angina with dysp- nea between the attacks. M. J. Breit- man (Vratch, Nov. 14. 1900). Hysterical angina pectoris is common, especially before the age of 40. It is most frequent in women. The crises in childhood are less severe than those of adult life. Almost anything may be the cause of the attack, even acute articular rheumatism. Frequent parox- ysms are often noted about the meno- pause. Sometimes an attack occurs by suggestion from seeing a paroxysm in another. There is precordial pain, often with a distinct aura. The parox- ysms occur at night, periodically. About the precordia is generally found an area of marked hyperesthesia. Pal- pitation, rapid pulse, and vasomotor symptoms arc common. In fact the symptomatology is polymorphous. In some cases true aortitis or endocarditis may exist, yet the attacks of angina pectoris are hysterical. Mercklen (Medecine moderne, Apr. 23, 1902). Syphilis, — A history of syphilis in a man, even if under 40 years of age, renders the occurrence of true angina pectoris less improbable than it other- wise would be, for there is a possibility of syphilitic aortitis obstructing the ori- fices of the coronaries. Tobacco, Tea, etc. — Excess in to- bacco (less often alcohol, tea, and cofTee) and lead poisoning may occasion spurious angina, or again they may aggravate a genuine paroxysm depend- ing on organic lesions. ANGINA PECTORIS (VICKERY). 675 While certain cases are evidently true angina and others equally ob- viously pseudoangina, some are ex- tremely puzzling. All these attacks (true and "false") have this much in common, that for the time being the heart is unable to perform the work demanded of it; so that they differ more in etiology and prognosis than in immediate condition. ETIOLOGY. — -Males over 40 years of age in comfortable worldly cir- cumstances make up the majority of sufferers from angina pectoris. Pre- disposing causes are: alcohol, syph- ilis (arterios-clerosis, ta1)es dorsalis). rheumatism, gout, diabetes, chronic nephritis, and bacterial infection (in- fluenza, plague, malaria). Sometimes attacks are hereditary. As exciting causes may be named : physical exertion, mental strain, pro- found emotion, and digestive disturb- ances. The writer observed several cases of angina pectoris, in which hyper- acidity of the gastric secretion was shown by an Ewald and Boas test breakfast with a bland meal taken the previous evening, and usually a glass of milk before retiring. These cases may explain the anachronism of an epigastric or abdominal angina pec- toris, both an impossiljility. He re- calls Latham's view that angina pec- toris is a cramp of the heart, excited by the hyperacid gastric juice through the filaments of the vagus; a fact which should not appear strange to any one familiar with the violent spasms excited by hyperacid secre- tion in spasmodic closure of the py- lorus. This cardiac spasm may supervene in any and all the various forms of cardiac disease, which ex- plains the many contradictions set forth 1)y Allbutt. 11. Tlloway (N. Y. Med. Jour., May 25, 1918). The attacks may appear in the daytiiue, especially at first; but some of the worst occur at night; so that finally the patient may dread going to sleep. A point that stands out prominently in the writer's experience is the fre- quency of angina pectoris in physi- cians. Thirty-three of his patients were physicians, a larger number than all the other professions put to- gether. Only 7 were al)ove 60 years of age, one a man of 80. with aortic valve disease. The only compara- tively young man in the list, 35, was seen nearly twenty years ago in an attack of the greatest severity. Worry and tobacco seem to have been the cause. He has had no at- tack now for years. Two cases were in the fourth decade, 13 in the fifth, and 11 in the sixth. Neither alcohol nor syphilis was a factor in any case; of the 26 patients under 60, 18 had pronounced arteriosclerosis and 5 had valvular disease. In a group of 20 men, every one of whom Osier knew personally, the outstanding feature was the incessant treadmill of practice, and yet every one of these men had an added factor, worry. So far as symptoms are concerned, the writer's cases fall into three groups: 1, Ics formes fntstes; 2, mild, and, 3, severe. 1. The mildest form, "Ics formes frustcs" of the French, with substernal tension, uneasiness, distress, rising gradually to positive pain, is a not in- frequent complaint, one, indeed, from which few escape, is associated with three conditions. Emotion is the most common and the least serious cause. 2. Under the mild form, angina minor, come 43 cases. Osier has grouped under these the neurotic, vasomotor, and toxic forms, the vari- eties which we formerly spoke of as false, or pseudo-, angina. The special features of this variety are: the greater frequency in women, the milder character of the attacks, and the hopeful outlook. 3. Severe angina, angina major, is represented by 225 cases, of which 676 ANGINA PECTORIS (VICKERY). 211 were in men. Two special fea- tures here are, existence in a large proportion of all cases of organic change in the arteries and liability to sudden death. Osier (Jour. Amer. Med. Assoc, from Lancet. Mar. 12, 1910). Angina from tobacco can be agon- izing, but it always ceases with the withdrawal of the narcotic; where the angina persists despite this with- drawal, it is necessary to make a Wassermann test for syphilis. Three cases reported in which a positive re- action indicated the proper mercurial treatment, which was followed by immediate relief after other measures had proved inert. C. Feissinger (Semaine med., Apr. 2. 1913"). The angina pectoris following over- exertion is merely a primary dilata- tion of the left heart when the heart has been "forced." Tobacco can only evoke an attack with hitherto latent organic trouble, but is not capable of inducing the latter. Huch- ard found a history of syphilis in 35 of 150 cases of angina pectoris and the author in 30 of 100, and this be- fore the Wassermann reaction was known. H. Vaquez (Arch, des Mai du Coeur. Mar. -Apr.. 1915). An analysis of 17S cases showed that the great majority of them oc- curred between the ages of 55 and 64. In 26 per cent, no definite lesion was detected either in tlie heart or in the aorta. In 24 per cent, there was a valvular lesion, and in 25 per cent, there were aortic dilatation and aneu- rism. Bramwell (Edinburgh Med. Jour., Dec. 1915). PATHOLOGY.— It is exceptional for attacks of true angina pectoris to be observed in persons presenting no evi- dence of organic circulatory lesion. The commonest underlying conditions are sclerosis of the coronary arteries, degeneration of the myocardium, car- diac hypertrophy, atheroma of the aorta, aneurism of that ves.sel near its origin, and aortic regurgitation. There is, however, "hardly an afifection of the walls or cavities of the heart, scarcely a morbid condition of the arteries that nourish it or spring from it, with which the distressing malady has not been observed to be associated" (Da Costa). Recent writers lay stress on oblitera- tion of the lumen of the coronary arter- ies as the essential basis of true angina pectoris, which obliteration may be oc- casioned either by sclerosis of the ves- sels or by changes in the aorta at their origin. "So intimately associated is the true paroxysm with sclerotic conditions of the coronary arteries that it is ex- tremely rare apart from them" (Osier), lluchard held the same view. The pain of angina depends upon vascular distention in the mediasti- num, which is the result of a more or less localized vasodilatation and of a more or less generalized peripheral vasoconstriction. It would seem that the angina is not due to the organic lesions any more than is asthma due to emphysema, or migraine to athe- roma of cranial vessels. The con- nection between the organic lesions and angina should then be ascribed to the chronic peripheral vasocon- striccion, which constitutes the ear- liest stages of many forms of chronic organic disease of the heart and vessels. Preventive treatment resolves itself into the prevention of exaggerated peripheral vasoconstriction, continu- ous or recurrent. Purin-free diet, cutting down of the intake of carbo- hydrates, especially the saccharine carbohydrates, and the fats, is advo- cated. Francis Hare (Med. Rec, Oct. 20, 1906). Angina results from an alteration in the working of the muscle-fibers in any part of the cardiovascular sys- tem, whereby painful afferent stim- uli are excited. Cold, emotion, toxic agei*s interfering with the orderly action of the peripheral mechanism, increase the tension in the pump walls or in the larger central mains, causing strain, and a type of abnor- ANGINA PECTORIS (VICKERY). 677 mal contraction enough to excite in the involuntary muscles painful affer- ent stimuli. Mackenzie suggests that there is rapid exhaustion of the func- tion of contractibility, which is. after all, only the fatigue on which Allan Burns laid str'-ss. In a disturbance of this Gaskellian function is to be sought the origin of the pain, whether in heart or arteries. In stretching, in disturbance of the wall tension at any point, and in a pain-producing resist- ance to this by the muscle elements lie the essence of the phenomena. In a man with arteriosclerosis and high pressure, and all the more likely if he has a local lesion, a syphilitic aortitis for example, disturbance, at any point, of the tension of the wall permits the stretching of its tissues. Spasm or narrowing of a coronary artery, or even of one branch, may so modify the action of a section of the heart that it works with disturbed tension, and there are stretching and strain sufficient to arouse painful sensations. Or the heart may be in the same state as the leg muscles of a man with intermittent claudication, working smoothly when quiet, but in- stantly an effort is made, or a wave of emotion touches the peripheral vessels, anything which heightens the pressure and disturbs the normal contraction brings on a crisis of pain. Osier (Lancet, Mar. 26, 1910). The writers observed a man of 34, who developed attacks of angina pec- toris and died in 5 months. There was no trace of venereal disease or alcoholism, but signs of tobacco pois- oning had been so pronounced that his daily ration of cigars and cigar- ettes was reduced. The case would have been cited as one of fatal tobacco poisoning but necropsy re- vealed syphilitic lesions in the aorta partly closing up the openings into the coronary arteries. Mouriquand and. Bouchut (Arch, des Mal. du Coeur, Oct.. 1912). The writer does not deny all sig- nificance to the prevailing doctrine of coronary sclerosis, but its meaning has hitherto been virtually negative. The hypothesis of Mackenzie is un- tenable. Angina pectoris does not mean a want of muscular strength, of contractility, but the result of "brus- que hypertension in the left ventricle, both systolic and diastolic from the increased tone, together with an un- regulated and disordered excitability" of the "primitive fascia and of the cardiac nerves." Castelli (Riv. criL di clin. med., Dec. 6, 1913). Heberden — who introduced the name of angina pectoris for the affec- tion— declared in 1768 that its most common termination is sudden death. This holds good today, yet we are unable to state the rationale. In 1889 McWilliam advanced the belief that in many cases of sudden death a mj-ocardial fibrillation could be in- voked as the efficient cause; but only recently have animal experiments given some corroboration to this view. Sudden death in angina pec- toris is considered by the writer to be the result of ventricular fibrilla- tion, but the direct actual proof can be supplied only by electrocardi- ography. The patient does not die from paralysis of the heart but from the direct opposite, the excessive production of impulses. We already' have data which shows that angina pectoris occurs only when there is temporary ischemia of the heart, and we know by experiments on animals that this ischemia is liable to pre- cipitate fibrillation of the ventricles, and also that the ischemia predis- poses the heart to fibrillation. Her- ing (Miinch. med. Woch., Nov. 2, 1915). The immediate, precipitating condi- tions of a paroxysm are not known, but they are supposed to be connected with disturbances of the vagus, or, perhaps, the sympathetic nerves. Nothnagel re- ported a series of cases under the title "angina pectoris vasomotoria" which seemed to be due to a pure neurosis. They followed exposure to cold, and were ushered in by spasm of the pe- ripheral arterioles, which presumably 678 ANGINA PECTORIS (VICKERY). produced tlie cardiac disturbance be- cause of the increased exertion de- manded of the heart in order to propel the blood through narrowed channels. Broadbent describes angina vaso- motoria as a comparatively favorable class of cases of high arterial tension associated with general arteriosclerosis and a hypertroj)hicd heart capable of powerful contraction. ' "The circulation in tlie coronary arteries may be suffi- cient for ordinary needs, but when the arterial tension is further raised by exertion or increase of peripheral re- sistance attacks of angina are induced." From a neuralgia or a neurosis true angina pectoris differs in being fre- quently fatal, in attacking men ten times as often as women, and in being associated with organic changes in the neighboring structures, viz. : the heart and aorta. Lesions of the cardiac plexus and the branches of the vagus have been found in repeated instances of angina pectoris, but that such lesions are invariably pres- ent and essential to the disorder has not yet been proved. "'Flic cardiac nerves may be seriously implicated in aneur- ism, in mediastinal tumors, in adherent pericardium, and in the exudate of acute pericarditis, without causing the slightest pain" (Osier), The late Sir Benjamin W. Richard- son regarded angina pectoris as an actual disease analogous (as Trousseau held) to epilepsy, and due to a disturb- ance in the sympathetic nervous system. Attention called to the coincidence of disturbances in circulation else- where. In a man of 33, angina pec- toris, Raynaud's disease, loss of 1 eye from disturbance in the circula- tion in the retina, and intermittent claudication occurred in turn. The first symptoms were an attack of angina pectoris after a bombardment. These conditions were all on the left side, a fact which points to a nervous origin for them all, and seems to ex- clude local endarteritis. The attack in the fingers was brought on by cold, the attack in the toe by walk- ing, the angii.a pectoris by fatigue and emotions. The fatal outcome in this case shows that even attacks with a nervous origin may prove fa- tal and that spasm of the artery cap- able of producing total anemia in a finger can well arrest the heart. Bard (Presse med., Jan. 26, 1921). Debove says that in tabetic angina pectoris there is no organic lesion of the heart or large vessels, and that the at- tack must be regarded as a visceral crisis. Dana refers cardiac crises in tabes to a degenerative irritation of the vagus. It should, however, be reinem- bered that aortic disease is rather fre- quent in tabetic patients. In regard to tlie causation of attacks of angina pectoris in the graver cases which are associated with serious struc- tural disease of the heart and vessels, J. Burney Yeo states that in by far the greater number of deaths from organic disease of the heart all the various lesions may be present which have been found in fatal cases of angina and yet no true anginal attacks have ever been complained of. In his opinion there is some additional circumstance needed to account for the angina. The most serious forms of angina seem to have a complex causation. First, there must be a neurosal clement ; the nerves of the cardiac plexus suffer irritation, and an intense cardiac nerve-pain is excited ; this acts as a shock to the motor nerves of the heart, and thus reacts on the heart-muscle, which, in fatal cases, is already on the verge of failure from organic causes; and, if there shotild be excited at the same time some reflex arterial spasm, the heart will have to ANGINA PECTORIS (VICKERY). 679 encounter an increased peripheral re- sistance as well. In such cases the rapidity of the fatal issue is no argu- ment against the neuralgic nature of the angina. In certain conditions, espe- cially in habitual high arterial tension, strain is apt to fall (when the aortic valves are competent) rather on the first part of the aorta than on the ven- tricular surface, and anginal attacks are more prone to occur in these cases, as this part of the aorta is in such close relation with the nerves of the cardiac plexus, rather than in those cases in which the strain is felt on the interior of the cardiac cavities. The causation of the less grave and more remediable forms of angina is also, in many instances, complex. A cardiovascular system feeble and poorly nourished on account of anemia may be submitted to undue strain; or there may be some intoxication — such as that of tea, tobacco, alcohol, gout, or some intestinal toxin — irritating the cardiac and vasomotor nerves, increas- ing peripheral resistance, and so ex- citing anginal attacks, which may alto- gether pass away and be completely recovered from. Vasomotor spasm as a unique cause of attacks of angina must be set aside as inconsistent with extended clinical experience. Cases of angina pectoris, both of the milder and graver forms, occur without any evidence of vasomotor spasm or of heightened arterial tension; and the conditions of heightened arterial ten- sion, together with a feeble cardiac mus- cle, very commonly coexist, without any tendency whatever to the develop- ment of anginal attacks. The argument in favor of a vasomotor causation has been inferred from therapeutic experi- ment and the relief to the paroxysm which has attended the use of agents which cause arterial relaxation. But most, if not all, of these vasodilators are also anesthetics, and, as Balfour has pointed out, it is probably to their anodyne action on the sensory cardiac nerves that they owe their chief effi- cacy ; Grainger Stewart also has pointed out that nitrite of amyl has a direct efifect on nervous structures, and that it relieves other forms of neuralgia. Certain fallacious conceptions of angina pectoris prevail. Thus, in true cardiovascular angina pectoris, peripheral arterial sclerosis, cardiac hypertrophy, and high blood-pressure are essential. This is by no means always the fact. Arterial change may be widespread and the coronaries sclerotic without hypertrophy of the heart or rise in blood-pressure. The sclerotic or atheromatous process may be quite limited, localized to the begin- ning of the aorta, and only encroaching a little on the coronaries, while the pe- ripheral vessels may be normal. Espe- cially in syphilitic cases are the condi- tions liable to be thus localized. In some of the most serious cases there may be no abnormal arterial pressure, indicat- ing, perhaps, a weakened cardiac muscle. The finding of aneurism or lesion of the aortic valves does not exclude angina, but is rather in its favor. The attacks are not always few in number, and fol- lowing exertion, and life is not neces- sarily cut off within a fevv months after the appearance of the disease. Patients may live a number of years with com- paratively frequent attacks. While com- paratively rare in women, the disease is by no means unknown, and serious mis- takes may be made in diagnosis, espe- cially in nervous and hysterical cases. The cardiopath is often a neuropath also. Pain is not always excessive. It may be mild or even lacking: its radia- tion is variable. Even in fatal cases there may be no constant pain. Uncon- sciousness, though unusual, is seen at times, and, while the patient usually is afraid to move, and will not lie down, there are exceptions to this rule. Eruc- tations or vomiting during an attack do 680 ANGINA PECTORIS (VICKERY). not prove it to be a false angina and not organic or cardiovascular. While the disease is very grave, there is no certainty that death is imminent. The kidneys, as well as the heart, must be investigated as regards prog- nosis. J. B. Herrick (Jour. Amer. Med. Assoc, Oct. 22, 1910). PROGNOSIS.— The underlying condition is apt to prove fatal event- ually, and it may end life in the first paroxysm ; but a careful regimen may prolong existence for years, and Flint, Bendel, and Labolbary have each re- ported cases of recovery. The signs of danger during any par- ticular attack are the subjective sense of impending death and the feebleness and irregularity of the pulse. The gen- eral prognosis is. of course, influenced by the stage which the organic circula- tory changes have already reached. The pseudoattacks are apt to be repeated oftener than are the genuine, but the prognosis is good, both as to life and as to the final disappearance of the trouble. In common with all other observ- ers, the writer iinds that angina pec- toris is more common in the male than in the female, in the ratio of 63 to 48. The youngest patient in his series of cases was 29 years old; the oldest, 76. The longest duration of the recurring syndrome was seven- teen years; the shortest was found in three who died in the first attack. In the cases of angina in which coronary sclerosis alone existed we find 3 dead in the first attack and 7 others dead. Of the latter, 2 died of diabetic complications, 1 of compli- cating pneumonia in the status an- ginosus. death being due to acute car- diac dilatation, 1 of a cerebral and another of a gastric hemorrhage. So that, in all, in only 6 cases could death be attributed to the coronary sclerosis. The duration of the dis- ease in these cases varied from six- teen months to seventeen years, and all were males. In the 29 cases of coronary sclerosis there is but 1 fe- male. When the obstruction is due tj thrombosis or embolism, the attack is usually fatal, either immediately or later on, as the result of changes in the myocardium. The attack is al- ways immediately fatal when one coronary artery is closed. As a rule, death occurs instantaneously where the descending or circumflex branches are completely closed, but occasionally the patient survives for a few days, as is shown by myocardial infarcts found post mortem. Forchheimer's ex- perience leads him to believe that when both cardiac asthma and an- gina pectoris are present from the onset the outlook for improvement is very small. But he does not agree with Xeubiirger, who states that in coronary sclerosis there are 3 stages of myocardial changes, which de- velop and vvhich are always fatal. So far as the duration of the dis- ease is concerned, aside from those who died in the first attack, jn 8 the disease lasted from one to two years; in 4 from two to four years, and in 1 for seventeen years. Of those alive, 4 have had the disease from eight to ten years, the same number from five to eight years, and 10 from four to five years. F. Forchheimer (Jour. Amer. Med. .'\ssoc., from III. Med. Jour., May, 1910). TREATMENT.— During a parox- ysm the first remedies to employ are such as will dilate tlie arterioles. Ni- trite of amyl is the best because it acts with the greatest rapidity. A "pearl'' of this drug may be crushed in a handkerchief or in cotton placed in the bottom of a glass tuinbler, and inhaled. Nitroglycerin may be in- jected subcutaneously (Koo to %o grain), or a tablet of this substance may be masticated, or a minim of spiritus glycerylis nitratis may be placed upon the tongue. It is readilv absorbed from the mouth and acts ANGINA PECTORIS (VICKERY). 681 almost as quickly as when given hypodermically. Erythrol tetranitrate has an action like nitroglycerin, but milder and decidedly more prolonged. It may be given in tablets of ^ to 2 grains. The nitrites are sometimes marvel- ously efficacious in checking an at- tack, and their failure to give benefit does not exclude true angina. In some cases digitalis does more good than all the nitrites or iodides, and in this the writer's experience agrees with that of Romberg, who advised it in some cases. J. B. Herrick (Jour. Anier. Med. Assoc, Oct. 22, 1910). The writer h «; long been convinced that the absorption of toxic products during metabolism is an etiologic factor of importance in the patho- genesis of all functional troubles of the heart and of the aorta. In 123 anginal patients, 80 of whom have been followed for a sufficient time to warrant therapeutic conclusions, diet- etic treatment intended to avoid toxemia was used. The first day, the patient having angina pectoris at- tacks is given nothing but water. On the second day milk is given in quan- tities varying from lyl to 3 quarts. Nothing but milk is allowed for from 1 to 3 weeks, according to the severity of the case and the response to treatment. In the milder cases, at the end of a week, soups made of milk and various kinds of cereals are added and continued for 1 or 2 weeks. At the end of this time cooked vegetables without salt are added and continued for a month or two. Then eggs and a small amount of meat are allowed. Milk still re- mains the basis of the diet, and no salt is added to the food. Soca (Arch. d. mal. du Coeur, Aug., 1915). The theory that the real seat of the disease is usually in the arterial walls and often in the external coat accounts for the incidence of the pain much better than the older view that the disease resulted from an afifec- tion of the coronary arteries with degeneration of the myocardium. The prognosis is more hopeful than is generally believed, under proper care and treatment, a very important part of which is abundant rest with heart tonics as needed. In the treat- ment, nitrates are among the most valuable remedies, but they are usu- ally given in insufficient doses. The sublingual administration of fresh hypodermic tablets of nitroglycerin is of great value in relieving pain. It is of the utmost importance that these tablets should be fresh and that they should be given in sufficiently large doses. Given sublingually, the full efi'ect of these tablets is experi- enced in from 1 to 3 minutes, where- as taken into the stomach the effi- ciency is reduced by half and the effect delayed for about 10 minutes. When an attack comes on 2 or more tablets of Koo grain (0.00065 Gm.) of nitroglycerin should be taken at once and repeated every few minutes until the desired effect is obtained. The effect of amyl nitrite is not as certain as nitroglycerin. Sodium nitrite seems to possess some toxic property and is liable to disturb the stomach. Erythrol tetranitrate was found to cause more headache and did not relieve the pain as promptly as nitroglycerin, although its effects may be of longer duration. The heart may be protected against in- hibition shock by the use of atropine in doses as much as %oo grain (0.002 Gm.) may be needed for some adults. E. Fletcher Ingals (Jour. Amer. Med. Assoc, Apr. 6, 1918). Relief by these means is often im- mediate; but, if not, ether should be inhaled. Chloroform is also advised by excellent authorities. Flint thinks it not without danger, if the heart is weak; ether, on the other hand, is a stimulant. Morphine, subcutane- ously, is a valuable and sometimes an indispensable remedy. Whittaker advises that it be given with cau- tion in a condition which may any- way terminate in sudden death. The 682 ANGINA PECTORIS (VICKERY). morphine (^ grain) may be guarded by atropine ('^o grain), and in case of alarm also by strychnine (V30 to Y20 grain). Electricity has also been recommended. Factors capable of bringing on the pain should be carefully avoided; every renewal of it keeps up the sum of stimuli. If for this end absolute stillness in bed be required, then bed it must be, with the corresponding reduction of food. If at first the at- tacks are not abolished, they will be mitigated, and will gradually taper off. All measures, medicinal, dietetic, etc., known to reduce arterial pressures should be enforced. Sir Lauder Brunton's potent means, the nitrites, are indispensable. To Ruard against vagus inhibition, atropine must be administered regularly. In very pain- ful cases morphine may be needed also. An ice-bag applied cautiously and intermittently to the upper tho- racic spine may prove helpful. The cause then requires treatment. Of new remedies two have seemed in the author's experience to be efficacious, more especially in angina minor — namely, (a) the high-frequency cur- rent, and (h) tlie administration of the lactic acid bacillus l)y the method of Metchnikoff. Baths and massage cannot be prescribed in any urgent stage of the disease. Causes of ec- centric irritation must be discovered and neutralized. The patient must be warned never to swallow quickly, nor to bolt large morsels. Diuretin and aspirin have their advocates. Chloroform is very dangerous in an- gina. In syncopic failure of the heart artificial respiration should be tried. .-Kllhutt (Brit. Med. Jour., Oct. 16, 1909). Although the writer applied the Wassermann test in many cases of true angina pectoris, he obtained a positive response in onlj^ 33 per cent. Yet, after treatment as for syphilis there were no further attacks in 90 per cent, of the cases. In some there was a slight return of the pains later, but they subsided anew on resump- tion of treatment. Arsphenamin should not be used, as it brings on serious disturbances with aortic les- ions. He obtained the best results with mercurial treatment in minute doses, on alternate days, in a series of 15 cases. Josue (Paris Med., July 5, 1919). Hot and stimulating applications over the precordia, such as a strong mustard poultice, are appropriate, as are also heat and friction for the ex- tremities. Sometimes an ice-bag is put over the heart. By some it is preferred to heat. Alcohol and aro- matic spirits of ammonia are of bene- fit in case the cardiac action is feeble. Syncope demands such drugs as digi- talin, caffeine, strychnine, and cam- phor, emplo} ed hypodermically. Good results obtained from theo- bromine in angina pectoris. In 1 case a man of 46 had been suffering for 2 months from repeated attacks of angina pectoris, recurring so con- stantl}' that he did not dare to go to bed; the attacks only lasted a few minutes, but had already induced great debility and distress. Exam- ination revealed insufficiency of the aortic valve. He was given 0.5 Gm. (7.5 grains) of theobromine, and the dose was repeated at bedtime. There were no further attacks then or later. The treatment with theobromine must be long kept up, for months and j'cars. Marchiafava (Policlinico, Feb. 28, 1909). Prolonged rest in bed advocated in true organic cases. Marked improve- ment noted in most Of the 20 cases studied. The patient should remain in bed at least 2 weeks, prolonged to 6 or 8 weeks in cases that cannot walk without bringing on anginal pain. Milk diet to be imposed from the start; later farinaceous foods added. Drug medication by theobromine, nitroglycerin, and even morphine and digitalin also utilized. Greatest im- provement in old patients and those losing weight during treatment; least. ANGINA PECTORIS (VICKERY). 683 in cases with associated aortic insuf- ficiency. Fiessinger (Bull, de I'Acad. de med., Nov. 29, 1910). The present writer has known oxy- gen to contribute to a favorable result in collapse due to chronic myocarditis with dilatation of the left ventricle, and it might be well for a subject of angina pectoris to keep some ready in his house. The painful attacks incident to car- diac disease, such as angina pectoris, also paroxj-sms of tachj-cardia, can be mitigated bj- causing the patient to belch up wind from the stomach, owing to the fact that the heart and the stomach are both innervated by the pneumogastric nerve. Eructation is produced by the following pro- cedure: The patient, seated, takes a small drink of water and holds it in his mouth. He then throws his head as far backward as possible and swal- lows the water. The posture is such as to stretch the esophagus and in- duce in the pharynx a sensation which causes eructation, provided the result is not voluntarily prevented by the patient. It is well to warn the person that an eructation is desired; otherwise, he may restrain it out of a sense of decency. Max I^erz (Semaine medicale, June 3, 1908). Dyspeptic disturbances are respon- sible for or at least aggravate angin.-t pectoris in many cases. Great benefit can be derived from magniesium oxide and peroxide to neutralize ab- normal production of gases and the gastric juice, and promote bowel functioning. Chlapowski (Aled. Klinik, June 5, 1910). Between attacks it is of vital impor- tance to avoid the predisposing and exciting causes. Rest and moderation are demanded, especially after meals. As for drugs, nitroglycerin, taken af- ter meals in doses just short of caus- ine headache, has a distinct inhibitorv effect upon the paroxysms. In some instances it might be better to order it every three hours, as its influence is not long continued. Nitrite of sodium (2 to 5 grains) may replace nitroglycerin. Laxatives and eliminative treat- ment by alkalies are often of great value. Surgical treatment of angina pec- toris is advocated by Jonnesco. The phenomena of angina pectoris are caused by irritation of the cardio- aortic plexus due to a constant lesion of the aorta. By breaking the cen- tripetal route between the cardio- aortic apparatus and the nerve cen- ters by resecting the cervical sympa- thetic nerve, the advent of the aortic reflexes in the nerve centers and the reaction of these centers can be pre- vented. The writer performed a resection of the left cervical sympa- thetic in a case ol angina pectoris. A definite cure resulted. Because of the brilliant result from the unilateral operation, he believes that a resec- tion on the left side will usually be sufficient, but as the operation is simple and harmless, it is preferable to perform it on both sides. T. Jon.- nesco (Presse med., xxix, 193, 1921). The persistent use of potassic io- dide is very eft'ective. Ten or fifteen grains may be given thrice daily before meals in half a glassful of water; or twenty grains three times a day for twenty days, followed by nitroglycerin for ten days. The io- dide is believed to dilate the arterioles and to promote arterial nutrition. See supposed that also by enlarging the caliber of the coronary arteries it in- vigorated the myocardium. Arsenic and phosphorus in small doses also tend to avert the parox- ysms. In case of fatty degeneration of the heart they would be contra- indicated. Barium chloride in doses of Yv.) to % grain after meals is a good tonic for cardiac inefificiency. and often relieves cardiac pain. 684 ANGINA PECTORIS (VICKERY). Quinine and methylene blue have also been recommended. The treatment l)y saline baths and by the Schott method of exercises has a most potent effect in improving the condition of the cardiac muscle and vessels, and appears to have a direct effect in making the attacks less numerous and severe, and even in causing them to cease during a period of months or years. The movements must i)e made with es- pecial care and caution in these cases, and the resistance at the onset must be at a minimum. The artificial saline l^aths should contain from 1 to 3 per cent, of salt, and from ^4 to 1 per cent, of chloride of calcium, and should gradually be strengthened by the addition of carbonic acid. Massage three times a week and persisted in for months may be of great benefit. In most cases it is best to prohibit alcohol. The cardiac tonics — sparteine, stro- phanthus, strychnine, valerian, and in suitable cases digitalis — are of the greatest utility. The general tendency to anemia and defective oxygenation must never be lost sight of, and general tonics, including tlie use of oxygen gas, will be of excellent service. Attacks of pseudoangina may be treated with asafetida, ammoniated tincture of valerian, or compound spirit of ether, and thr outward em- ployment of heat, friction, and rube- facients. Sometimes recourse must be had. hovk^ever reluctantly, to mor- phine. The statement in clear and decided language of a favorable prog- nosis is of great benefit. Between at- tacks the underlying condition should be carefully sought and treated. The frequent and indiscriminate use of such terms as false angina pec- toris, angina sine dolore, angina vasomotor, etc., gives no clear sense of their etiology or pathology. The treatment should be based on these as follows: — Hypertensive Cardiovascular Disease with Myocardial Insufficiency. — In this group the usual cardiac changes are ventricular hypertrophy, usually left, but sometimes right also; a patchy fibrous myocarditis; thickened aortal and mitral cusps; lime deposits on the first portion of the aorta and atheroma and thickening of both coronaries. There is a systolic blood- pressure of about 190 mm.; rough systolic first and sharply accentuated second sound at the right base; heaving apical impulse; urine with or without albumin or casts; varying grades of edema and visceral conges- tion; dyspnea usually upon excretion. The pains are commonly dull, most marked in the precordium and radiate to the neck and arms. As to the cause of the pain, it seems to be due to nutritional cardiac disturb- ance from inadeciuate coronary cir- culation. The author depends mainly on digitalis, preferably the tincture, given in 15-minim (1 c.c.) doses 3 times a day, continued even when pain and other symptoms disappear, for an indefinite period. Mental ex- citement and stress should be avoided. For the edema, theobromin sodium salicylate in 1-gram (15-grain) doses /. ;. (/.. on alternate days in water or in wafers are recommended. The Carrel diet was an excellent aid. In cases in which a luetic condition is proved or suspected the iodides are useful, otherwise they proved of no value in the relief of the pain. Hypertension and Myocardial In- sufficiency with Unstable Vasomotor Mechanism. — This is a smaller group with the highest systolic blood-pres- sure, around 180, and marked diurnal variations, precordial pains following exercise. Emphysema and myocar- ditis are the main pathological en- tities. Experimental subcutaneous ANHALONIUM LEWINII. 685 injections of nitroglycerin in doses of %o grain (0.0013 Gm.) t. i. d., has a marked temporarj' effect upon the blood-pressure and usually upon the symptomr. This or other vasodila- tors given at the onset of pain are likely to give great relief. Digitalis was not as beneficial as in Group 1. Uremic Group. — This group is char- acterized by headache, nausea, vomit- ing, varying grades of anemia, parox- ysmal, dyspnea, precordial distress, high systolic and diastolic pressure, nocturnal polyuria, and changes in the retina. The precordial pains are not relieved by nitroghxerin, digi- talis, or diuretin. The pains are ap- parently caused by retained excre- mentitious products in the circula- tion. Dietetic measures, especially low protein and high carbohydrates, are of most value. Acute Rheumatic Endocarditis and Rheunwtic Endocarditic Exacerbations. — These cases usually occur in young persons v^^ith mild tachycardia, no dj'spnea or decompensation, and with marked auscultatory evidence of val- vular disease, usually mitral stenosis. There were "sticking" pains in the heart itself, and usually, no Head's zones. The rapid heart action and the precordial pain seem due to fresh exacerbations of endocarditis. The best medication is sodium salicylate in 1-Gm. (15-grain) doses hourly until 6 doses have been taken or tin- nitus occurs. Bromides in moderate doses are helpful: absolute rest is necessary. General Circulatory Eailure and De- compensation from Endomyocardial Disease. — The cause of the precordial pain is apparently the nutritional disturbance in the heart, due to cir- culatory failure. Head's zones are often present. The treatment indi- cated for the first group is also indi- cated here. Embolic Infarcts in the Main Coron- aries and Their Branches. — In several cases with intermittent pains lasting days or weeks, the symptoms were possibly caused by embolic infarcts of the coronaries of the second or third order. There was a rise of temperature, acute endocarditis, pro- gressive tendency of the disease, and tender local precordial areas. Cardiac Lues. — This is a very fre- quent cause of precordial pain. The latter is usually substernal, dull, boring, and aching. It may, how- ever, have the distribution of the types already described. Head's zon?s are rare. The main patho- logical changes occur in the aorta and myocardium. Salvarsan com- bined with the usual mixed treatment is of great value. Premature Arteriosclerosis. — This rare group found in young adults, is characterized by persistent precor- dial distress, lasting often for months. Gastric symptoms similar to those of hyperacidity may predominate. Physical examination affords no hint of the severity of the pathological process. The cause for the sclerosis is still undetermined, but it may be the result of some infection and toxemia. E.xcept digitalis for tem- porary relief, treatment is of no avail. Tabacism. — The pains may be dull and aching, or sharp and radiating. The first premonition may be very sharp lancinating precordial pains radiating to the left shoulder and forearm and accompanied by uncon- sciousness. Most tobacco pains and arrhythmias cease when smoking is stopped. Occasionally they recur. Nitroglycerin given regularly or with the onset of pains is sometimes of benefit. S. Neuhof (Med. Rec, Jan. 15. 1916). Herman F. Vickery, Boston. ANGIOMATA. SELS, Tumors of. See Blood-ves- ANGIO NEUROTIC EDEMA. See Ascites and Edema. ANHALONIUM LEWINII (Mescal Button). — The mescal button is obtained from a plant growing in the val- ley of the Rio Grande, in Mexico. The 686 ANH ALCJX J L'M LEW I N 1 1 . plant is of the family Cactacese. The tops of the plant wlien dried constitute the commercial Anhalonium Lewinii, hrst in- troduced by Lewin. The buttons or seeds are brownish in color, shaped like a top, and from 1 to l^j inches in diameter. They are hard and can be pulverized in the mortar only with difficulty. In the mouth, however, under the action of the saliva, they swell and rapidly become soft, imparting a bitter, nauseous taste and causing a marked sensation of tingling in the fauces. Four alkaloids, — mescaline, anhalonine, anhalonidine, and lophopho- rine, — closely similar in their physiological effects, have been extracted from this species of anhalonium. From the related plant Anhalonium Williamsi the alkaloid pellotine is derived. PREPARATIONS AND DOSE.— The following preparations may be used: Tincture (10 per cent.); dose, 1 to 2 drams (4.0 to 8.0 c.c). Fluidextract (100 per cent.); dose, IVi to 15 minims (0.5 to 1.0 c.c). Powder; dose, 7K' to 15 grains (0.5 to 1.0 Gm.). The tincture and fluidextract should be made according to the processes prescribed in the United States Pharma- copccia for such preparations. PHYSIOLOGICAL ACTION.— Lewin found anhalonium to be an intensely poisonous drug. A few drops of the de- coction used by him in the frog sufficed to produce almost instantly changes consist- ing chiefly in the appearance of shrinking of the body, so that the batrachian seemed to pass into a mummified condition. Simultaneously, tlie animal raised itself upon its extremities and remainetl stand- ing in this position like an ordinary quad- ruped, or crawled about. After fifteen minutes this spastic condition passed off nnd the frog rapidly returned to the nor- mal state. When larger amounts were given death occurred in tetanic rigidity. The sj'mptoms produced seemed closely allied to those of strychnine, Lewin noting that even after the spinal cord was sev- ered peripheral irritation induced tetanus. Tn pigeons it was found that the drug pro- duced convulsive vomiting in a few mo- ments when injected hypodermicallj'. The bird spread its wings, crouched down to the ground, and when disturbed exhibited muscular twitchings. Later the head was drawn sharply back, tlie mouth opened widely, and general convulsions appeared. When death occurred the heart was al- ways found in diastole. In rabbits the sj-mptoms resembled those of strychnine poisoning. In the human subject anhalonium in large doses produces an effect in some ways closely resembling that of Indian hemp: visions ranging from flasiies of color to beautiful landscapes and figures, illusions of time and space, etc. This and related plants are employed as intoxicants by certain Mexican Indians in connection with religious ceremonies. According to Prentiss and Morgan, color effects consti- tute the main feature of tlie drug's action on tlie Ijrain. Consciousness remains un- impaired throughout its effects. Mitchell states that sometimes symptoms resem- bling the visual phenomena of ophthalmic migraine are experienced. The after- effects were also found by him to be markedly unpleasant, nausea and headache appearing which lasted for several hours. Ilcffter in 1898 carried out investigations en himself with the object of determining which of the active ingredients of mescal produced the visual hallucinations. An alcoholic extract of the buttons equ'valent to 4,'2 drams was taken, and afterward a corresponding amount of each of the alka- loids. The symptoms produced both by the alcoholic extract and by mescaline (1^2 grains) were colored visual hallu- cinations, slowing of the pulse, pupillary dilatations, loss of time relations, heavi- ness of the limbs, nausea, and headache. Anhalonine and anhalonidine in like amounts induced sleepiness without visual phenomena, while lophophorine (-Ko grain) caused occipital headache, facial redness and burning, and a temporarj- slowing of the pulse. Mescaline was thus shown to be the active constituent of anhalonium in respect of the visual phenomena. According to Dixon, who carried out careful pharmacologic studies of anhalo- nium in frogs, cats, and rabbits and wit- nessed its effects in man, the chief effects of the drug in therapeutic doses appear to be: (1) Direct stimulation of the in- tracardiac ganglia; (2) initial slowing of the heart; (3) elevation of arterial tension; (4) direct stimulation of the brain centers ANIMAL EXTRACTS (SAJOUS). 687 ijud of the motor spinal centers, as shown by an increase in reflex excitability. Full doses of anhaloiiium induce motor V eakness and inco-ordination. In still larger doses difficulty of respiration ap- pears. Lethal doses, Dixon found, pro- duce complete paralysis, and death is caused by respiratory failure. THERAPEUTIC USES.— Prentiss and Morgan employed anhalonium in various conditions dependent upon excessive nerv- ous iritability, with considerable success. While not a hypnotic in itself, the drug in therapeutic doses (7 to 15 grains) often removed the cause of the insomnia, and thus conduced to natural sleep. It has been credited with beneficial effects, espe- cially in neuralgic headache, acute de- lirium, mania, melancholia and hypochon- driasis, hysteria, irritative cough, and colic. Anhalonium tincture in drop doses has been claimed to be useful as a sus- tainer of the heart action. But little knowledge of its clinical value in circu- latory disorders has as yet, however, been obtained. According to Landry, the drug is a useful adjuvant to digitalis. The taste of the liquid preparations of anhalonium is bitter and unpleasant, but can readily be disguised. Lewin recom- mended for this purpose the use of fluid- extract of licorice and elixir of yerba santa (fluidextractum eriodictyi). The powdered drug may be administered in capsules or cachets. The chief untoward action to be feared in the event of excessive dosage of this drug is respiratory depression. S. ANHIDROSIS, or ANIDROSIS. See Sweat Glands, Diseases of. ANIMAL EXTRACTS, OR ORGANOTHERAPY.— Owing: mainly to the fact that physiologists even at the present writing (1921) have failed to discover the functions of any ductless gland, despite consid- erable effort to do so, empiricism still prevails to a very large extent. Textbooks of therapeutics and prac- tice still adhere to the convenient statements that an organic prepara- tion "is useful." that "it is recom- mended,"' or "has proven valuable" in this or that disease ; that is to say, without attempting to define its mode of action. The cause of this is not difficult to find : So many assump- tions as to the actual functions of the organs used therapeutically have been vouchsafed on totally inadequate ex- perimental evidence that textbook authors adopt none. The writer of the present article has taken another course. Rejecting all assumptions based on inadequate ■data, he has done his own experimen- tal work and used data froin oil branches of medicine, clinical and auxiliary, as a foundation for his own dediictions. Time has sanctioned this course. The conclusions he pub- lished in the earlier editions of his "Internal Secretions," and elsewhere, have steadily gained adherents, sup- ported as they have been by an in- creasing number of confirmatory facts contributed independently by experi- menters and clinicians. He feels it his duty, therefore, to adopt his own views as the foundation of the sum- mary of organotherapy submitted, knowing that they will best subserve the interests of the practitioner. The human body is managed by the endocrine glands of the body. Every individual from the time he is born until the time he dies is under the influence of these many different kinds of elements — some of them having to do with the development of the bones and teeth, some with the development of the body and nerv- ous system, some with the develop- ment of the mind, etc., and, later on — with the introduction of sex fea- tures— with reproduction. Still later on, these elements have to do with the preservation of these structures and functions which constitute the 688 ANIMAL EXTRACTS (SAJOUS). body and mind, and if these glands become under- or over- active there is a disturbance of the specific func- tions which these component parts are supposed to perform; and since these glands are dependent on each other, the upset of one disturljs the rhythmical action of the others. In recent years our knowledge as to the physiology of the ductless glands has been put to the test by endocrine therapy, and there is no longer any doubt that the future of medicine lies along these lines. In the writer's practice, endocrine ther- apy has displayed and replaced the old time drugs, so that practically 90 per cent, of all prescriptions for in- ternal use consist almost entirely, if not wholly, of endocrine extracts. The varying forms of amenorrhea, most of the menorrhagias and met- rorrhagias, threatened miscarriage, habitual miscarriage, sterility, the dis- orders and disturbances of the cli- macterium, and many other states met with in gynecological practice may be corrected in many instances specifically by a certain extract; in many other cases, by a combination of extracts. S. W. Bandler (Med. Record, Mar. 15, 1919). Instead of using the extracts of or- gans the venous l)lood issuing from the organ should be used. This con- tains the true internal secretion while the cells of the organ cease secreting this product when they are dead. Hence the removal of the organ from the body to make the ex- tract not only arrests production of the internal secretion but probably modifies essentially the delicate se- cretion already on hand in the tissues of the organ. Instead of a living se- cretion only a dead and possibly de- composed product is obtained. The efferent blood contains the secretion in its maximum vital potency. In 1911 the writer published researches on the thyroid secretion thus ob- tained in the efferent blood, and in 1913 and 1915 similar researches on the venous blood from the supra- renals, pancreas, and testicles. Man- fredi announced in 1913 that the ef- ferent blood from the pancreas in- hibited certain actions of epinephrin. He cites further researches since by Ollini, Masera, Durand and 8 others. The difficulty in obtaining the effer- ent blood or lymph hampers and limits the research in this line, but this should be the goal toward which we strive. G. Ghedini (Jour. Amer. Med. Assoc, from Gaz. degli Osped. e delle Clin., Jan. 5, 1919). Clinical, anatomic, histologic and bacteriologic observations led the writer to conclude as follows: The absence of certain accessory food fac- tors from the dietary — improperly termed "antineuritic" — leads not only to functional and degenerative changes in the central nervous system, but to similar changes in every organ and tissue of the body. The morbid state to which their absence gives rise is not a neuritis. The symptom complex resulting from the absence of these substances is due (a) to a chronic inanition; (b) to derangement of function of the organs of digestion and assimilation; (c) to disordered endocrine function ; (d) to malnutri- tion of the nervous system, and (e) to hypersuprarenalinemia. Certain organs undergo hypertrophy; others atrophy. Edema has invariably (1(X) per cent.) been associated with great hypertrophy of the suprarenal glands, while 85 per cent, of all patients hav- ing great amount of epinephrin in such patients as determined by phys- iologic methods, has been consider- ably in excess of that found in nor- mal suprarenals. Inanition gives rise to a similar state of suprarenal hy- pertrophy, and to a similar state of atrophy of other organs, the brain excepted. The edema of inanition and of beriberi is believed to be in- itiated by the increased intracapillary pressure which results from the in- creased production of epinephrin, act- ing in association with malnutrition of the tissues. R. McCarrison (Brit Med. Jour., Feb. 15, 1919). Since the internal secretions and their hormones have been definitely ANIMAL EXTRACTS (SAJOUS). 689 connected with the general protective the healthy gland in a dog shortly after thyroidectomy had been performed prevented the cachexia strumipriva and violent nervous phenomena which follow this operation. Then followed, in 1882, the labors of the brothers Re- verdin, succeeded, in turn, one year later by those of Kocher, of Berne, demonstrating that, in man as well as and auxihary— and from coordinated i" animals, the same phenomena oc- curred under identical circumstances. The principal postoperative symp- toms noted were: marked weakness and fatigue ; a sensation of cold, pallor, hardness, and dryness; ede- mechanism of the body, they form the systemic immunizing mechanism of the organism. In reaching this conclusion so pregnant with proba- bilities that internal medicine as a whole will be completely revolution- ized, Sajous, for more than a score of years, has by his conscientious labors, analj'sis of all reliable data derived from all sources — medical sj-ntheses of all factors entering into the problems, reached conclusions which have filled many obscure la- curur, and bid fair to make a logical whole of what now, in medicine, is decidedly chaotic. While these hor- mones are the active defensive agents matous swelling, thickening of the and their efficiency controlled by pharmaco-endocrinology, yet it may be that these same hormones may so increase the proteolytic activity of the digestive enzymes (defensive fer- ments) as to cause them not only to destroy pathogenic agents, bacteria, toxins, and certain other poisons, but also the blood cells (hemolj'sis) and even the tissues themselves (autol- ysis). The. recognition of this long con- tinued and constructive work has been recognized by the establishment of a chair of endocrinology at the University of Pennsylvania, where skin, and loss of hair, all with, as nervous phenomena: muscular stiff- ness and pains ; tetany, sometimes attaining the violence of true tetanus, and even clonic convulsions. The brothers Reverdin termed this condi- dition postoperative myxedema while Kocher called it cachexia strumipriva. The thyroid gland per se was subse- quently found to be responsible only for the myxedematous symptoms, however. The two external parathy- roids, discovered in 1880 by a Swed- he, as professor, with additional fa- ish physician, Sandstrom, and the cilities, may continue to add to the ^^^ internal parathyroids, discovered resources of scientific medicine. , y^ i i • • at- i c T> ^A \xr uu ^^T■^ /-ru ivf ^- i by a French physician, Nicolas, ot Reynold Webb Wilcox (The Medical -^ t- j ' Times, Jan., 1922). Nancy, in 1893, and independently by THYROID GLAND ORGANO- ^ohn, of Prague, in 1895, were sub- THERAPY.— In the latter part of sequently shown through the labors the last century. King, of London, of Gley, Vassale and Generali, Mous- showed experimentally that the colloid sous, Jeandelize. and others to be re- substance of the thyroid gland passed sponsible for the nervous phenomena, directly into the lymphatics. Schiff, of tetany, etc. Briefly, removal of the the University of Geneva, reviving thyroid alone arrested development views in 1859 previously held by many, and caused myxedema (cretinism in found that this organ played an im- the young), while removal of the portant part in the economy, through parathyroids alone was followed by some substance which it secreted, and tetany and early postoperative death, that intraperitoneal transplantation of The observation of Schiff, con- 1-^4 690 ANIMAL EXTRACTS (SAJOUS). firmed by other investigators, that graftiriL;" prevented the morbid effects of thyroidectomy as long" as the grafts lived, led ATurray and Ord to try the use of thyroid extract in myxedema. Not only was it found to counteract this disease by these clinicians and many others since, but thyroid gland, which includes parathyroid; but the latter alone, as will be shown under a special heading, also proved valuable therapeutical!}- in other disorders. How are these favorable phenom- ena brought about? PHYSIOLOGICAL ACTION.— In a recently published work on general therapeutics, one of tlie contributors states that : "the manner in which the thyroid gland presides over the nutri- tion of the b(^dy is unknown. It is generally admitted that it furnishes an internal secretion, that this secretion is formed by the living cells of the vesicles, and that it is poured into the colloid material they contain. But our knowledge," remarks the author, "has not advanced nuicli beyond this point." This naturally suggests a correspond- ing lack of knowledge concerning the physiological action of thyroid prepa- rations and their use as remedies. But here, as elsewhere in the realm of science, the world has not stood still. In truth, the last three decades have brought out facts which account not only for the nutritional phenomena witnessed under the influence of thy- roid preparations, however adminis- tered, but also for autoprotective or immunizing functions of the first order. ACTION ON METABOLISM.— Some physiologists hold that the thy- roid and parathyroids, by means of an internal secretion, "exercise an im- portant control over the processes of nutrition of the body," as Howell states ; others contend that the purpose of these organs "is to neutralize or de- stroy toxic substances formed in the metabolism of the rest of the body." Others again assert that it increases metabolic activity, especially catabo- lism. The one great factor which stays all progress in this connection is the persistent identification of these func- tions as separate entities, whereas they are in reality the manifestations of a single function. That such is the case is easily demonstrable : No one can deny that "the processes of nutrition of the body" represent a phase (that of anabolism) of the process of metabo- lism, nor can any one deny that catab- olism, the other phase of metabolism, serves to "neutralize or destroy toxic substances" formed in the body at large — and to break down fats, as is well known. If, therefore, the thy- roid secretion serves to activate ine- taboHsm, as first shown by two Italian scientists, Vassale and Gener^li. all the other processes mentioned are also in- tluenced by the thyroid. That such is the case has now been conclusively shown. [Chantemesse and Marie, Ballet and Enriques (cited by Popoff. Arch gen. de ined.. Oct.. 1899), Bourneville (Arch, de neurol., Sept.. 1896), and Shattuck (Bos- ton Med. and Surg. Jour., June 30, 1904), Lorand (Lancet. Nov. 9, 1907), and many other clinicians, including mj'self, have noted that tiiyroid preparations caused a rise of temperature of several degrees and that it took part in the febrile process. These observations were controlled by those of Stiive and Thiele and Xehring (Zeit. L klin. Med., xxx, p. 41, 1896), that th3roid extract increases over 20 per cent, the oxygen intake and to nearlj' as great a degree the carbonic acid output. This is evidently produced by the active agent of the thjToid secretion, iodine, for this halogen itself increases oxidation as well. ANIMAL EXTRACTS (SAJOUS). 691 Thus, Rabuteau, Milanese, and Bouchard (C.-r. de la Soc. de Biol., pp. 227, 12)7, 1873), Henrijean, and Corin (Arch, de pharmacodyn., ii, 1896) have all noted an increase of nitrogen excretion. Wood ("Therapeutics," 13th ed.. p. 499, 1906) and Cushny ("Pharmacology and Thera- peutics. 4th ed., p. 514. 1906) state, in fact, that iodine can produce fever. Removal of the thyroid, on the other hand, lowers oxidation. Albertoni and Tizzoni and Magnus Levy (Zeit. f. klin. Med., xxxiii, p. 269, 1897) found, for ex- ample, that this procedure decreased markedly the output of carbon dioxide, and that it caused hypothermia. The fall of temperature is gradual, according to Lorrain-Smith (Jour, of Physiol., xvi, p. 378, 1894), and most marked, according to Rouxeau (Arch, de physiol., xxix, p. 136. 1897), at the end of the operation. The proportion of red corpuscles is reduced, according to Moussu (C. r. de la Soc. de biol., p. 772, 1903). Reverdin observed in man that the hemoglobin was also dimin- ished, while Horsley noted increased sen- sitiveness to cold. Albertoni and Tizzoni and Masoin found that the blood con- tained less oxygen than normally. This applies as well to removal of the parathyroids, which was found by Jean- delize ("Insufificance thyroidenne et para- thyroidienne/' p. 45, 1903) also to lower the temperature. That tlie thyroid ap- paratus can itself raise the temperature, is shown b}^ the febrile process and sense of heat with flushing observed in the sthenic stage of exophthalmic goiter and when the thyroid apparatus is overactive when thyroid extract is given to such cases, the exchanges may be increased to a sur- prising degree — 77 per cent, in a case ob- served by Hirschlaff (Zeit. f. klin. Med., xxxvi, No. 3-4, S. 200. 1898-99). The last two decades have only served to confirm these observations. C. E. de M. S.] As urged by myself in 1903, the thy- roid enhances general oxidation and metabolism is partly due to excita- tion of the adrenals by the thyroid secretion contained in the blood. Star- ling has since (1906) termed "hor- mones" substances which thus act as stimuli to other organs, while Kraus and Friedenthal, Caro, Hoskins, and others have found (1908-1910) that thyroid extracts excited the adrenals. In addition to this, I attributed (1907) to the thyroparathyroid principle a di- rect action on the phosphorus of all tissue-cells (and particularly of their nuclei), the iodine found by Baumann to be the active agent, in organic com- bination, of the thyroid secretion (as well as of the parathyroids, as shown by Gley), rendering the phosphorus more susceptible to oxidation by the hemoglobin. [Telford Smith (Lancet, Oct. 7, 1897) and other clinicians have observed that the use of th\'roid preparations in young cretins was sometimes attended by softening of the bones and bending of the legs, notwithstanding marked general im- provement. When it is recalled that five- sixths of the inorganic matter of bone consists of calcium phosphate, it becomes a question whether the thyroid extract does not interfere with the building up of this tissue. That such is the case is fur- ther suggested by the facts that iodine, the active constituent of the thyroid secre- tion, and its salts, as shown by Henrijean and Corin {loc. cit.). Handheld Jones (cited by Wood, loc. cit.), and others, cause exces- sive elimination of phosphates and phos- phoric acid, and that thyroid preparations, according to Roos. Scholtz. (Central, f. inn. Med., xvi, pp. 1041. 1069. 1895). Pou- chet (Bull. gen. de therap., Sept. 15, 1905), and others, act in the same way. "Em- phasis must be laid.'" writes Chittenden (Trans. Congress Amer. Phys. and Surgs., iv, p. 93, 1897), "upon the apparent con- nection between the thj'roid gland and phosphoric acid metabolism," giving as example "the increased excretion of P2O.5 after feeding thyroids to normal animals, and the great decrease in the case of ani- mals with the thyroids removed." The untoward effects of large doses of thyroid preparations on the nervous sys- tem, owing to its wealth in phosphorus and fats as manifested by tremor, tachy- cardia, optic neuritis [Coppez (Arch. 692 ANIMAL EXTRACTS (SAJOUS). d'Ophtal., Dec, 1900) J. etc., also bespeaks such an action; Cyon (Arch, de physiol., X, p. 618, 1898), in fact, found that injec- tions of iodothyrin excited the depressor nerve directly to such a degree that the vascular pressure often declined to two- thirds of the normal. A familiar action of the thyroid prepara- tions is a rapid reduction of fat in obese subjects when full doses are administered. The presence in the fat-cell of a nucleus rich in phosphorus whose purpose is promptly to promote oxidation of the fat when the organism requires additional carbohydrates explains this action. Schon- dorff (Arch. f. d. gcs. Physiol., Ixiii, p. 423, 1896; Ixxii, p. 395, 1897), in fact, found that the reserve fats could be exhausted be- fore the nitrogenous tissues were aflfected. The mode of action of the thyroid active ])rinciple, iodine, is suggested by the pres- ence of this halogen in all nuclei, as shown by Justus (Virchow's Archiv, clxxvi, S. 1, 1904) and others. "If a frag- ment of phosphorus lying on a plate is sprinkled with iodine." writes Wilson ("Inorganic Chemistry." p. 284. 1897), "the substances unite, and heat enough is produced to kindle the phosphorus." Moreover. Roos (Miuich med. Woch., Xo. 47, p. 1157, 1896) found that in a dog in nitrogenous equilibrium, iodothyrin "caused at once a marked increase in the output of sodium, sodium chloride, and phosphoric oxide" (cited by Chittenden, loc. cit., p. 89). The experimental observations of Not- kin and White and Davies. and personal researches having suggested that the action of the adrenal secretion resembles that of an organised ferment. I termed it "thyroidase." C. E. de M. S.] The writers, using dogs, tried to de- termine the value of small doses of commercial desiccated thyroid gland, given by mouth, as a means of in- creasing nitrogen elimination. To eliminate the determination of a nitrogen intake, the dogs were given only sugar solutions, and their nitro- gen excretion, following the adminis- tration of the thyroid gland prepara- tions, was carefully studied and tab- ulated. Examination of the tables presented, which show the average nitrogen figures for 3 days preceding thyroid feeding and for the days of administration, and 2 days subsequent to it, indicate that a daily dose of 0.05 to 0.1 Gm. (% to V/2 grains) of desiccated thyroid mixture per kilo (2% pounds) of body weight is suffi- cient to produce a marked effect on the nitrogen elimination, with a some- what greater loss in weight than in the control animals. Rohde and Stockholm (Jour, of Biol. Chem., Feb., 1919). When in the light above, we admin- ister desiccated thyroid, which com- bines the actions of the thyroid and parathyroids, corresponding efifects are produced : It renders the phosphorus of all tissues, and all free substances, such as bacteria, wastes, toxins, etc., containing phosphorus, more inflam- mable or sensitive to the action of the oxygen in the blood. As this applies particularly to nerves and nerve cen- ters (all of which are especially rich in phosphorus), the adrenal center, and, therefore, the adrenals themselves, are excited, and, the adrenal secretion be- ing the agent which takes up the oxy- gen of the air to sustain the blood-oxy- genizing power, the supply of oxygen is also increased. All the various phos- phorus-laden substances are thus not only rendered more readily oxidizable by thyroid extract, but this remedy also provides indirectly the required oxy- gen. Hence also the familiar in- fluence of thyroid preparations on obesity, their action being mainly ex- ercised upon the nucleus rich in phos- phorus which fat-cells contain. The wonderful efifects of thyroid ex- tract in cretinism can also be readily accounted for: The rise of tempera- ture is due to the increased oxidation brought about by the thyroid and adrenal oxidizing substances acting jointly ; the enhanced metabolism is a ANIMAL EXTRACTS (SAJOUS). 693 normal result of the augmentation of general oxidization, while the increased appetite is due to the resuhing greater demand for foodstuffs. The marked improvement in general nutrition and strength is a self-evident result of the assimilation of a greater proportion of food materials, and the rapid growth likewise. The cerebrospinal system is particularly influenced owing to its wealth in phosphorus; hence, the devel- opment of intelligence. All organs be- ing the seat of active metabolic activity and nutrition, the intestinal, renal, car- diac, and cutaneous and hepatic func- tions are all enhanced. Even the hair grows, not only in cretinism, but when its loss is due to general adynamia. A slightly alkaline saline solution, or alcohol, extracts from the thyroid some non-coagulable material which is a vigorous stimulant for the gas- tric secretion. This material pro- duces its effects at least in part liy intensification of the functions per- formed by the terminal filaments of the (gastric) vagus. Extracts simi- larly made from the pathologic tis- sue of the adenomatous or hyper- trophied human glands are inert. Rogers, Rahe and Ablahadian (Amer. Jour. Physiol., Feb. 1, 1919). This, it must be emphasized, is the aggregate of effects obtained with small doses, at most, 1 grain of the desiccated thyroid (which represents 5 grains of the gland proper), three times a day. When larger doses are given another order of phenomena is awakened : those of excessive burning up. as it were, of the tissues. The inflammability of all phosphorus-laden elements being mark- edly enhanced while the quantity of oxidizing substance is as greatly in- creased, the tissue elements are broken down more rapidly than they are built up, beginning with the fats, and the patient becomes emaciated. THYROXIN.— Until recently the iodo- thyrin of Roos was deemed the probal>le active agent of the thyroid secretion, but the recent more precise biochemical re- searches of Edward C. Kendall, of Roch- ester, Minn., (Endocrinology, April, 1917, and April-June. 1918), have identified it as a crystalline compound containing iodine. The colloid of the thyroid was not found, as generally believed, to influ- ence the functions of the body at large. The crj'stalline compound referred to, "thyroxin," was found, even in small doses, to supplant thyroid activity, relieving myxedema and cretinism and in excess will produce symptoms of exophthalmic goiter. As little as 10 milligrams (Va grain) will, in fact, increase the metabolic rate 30 per cent. The name "thyroxin" is an abbreviation of "thyro-oxy-indol," the CO-NH group of which is thought to pro- duce physiologic effects with iodine prob- ably as an activator. The exact chemical reactions involved, however, are still sub judice but it is theo- retically attributed to an interaction be- tween thyroxin and an amino-acid, the function of the thyroid from this view- point being to furnish the animal organ- ism with ammonia resulting from the de- aminization of amino-acids, leading per- haps to the formation of urea. Antitoxic Function. — Another func- tion definitely credited to the thyroid gland is "to neutralize or destroy toxic substances formed in the metabolism" (Howell). Now tetany, as shown by the brothers Reverdin. we have seen follows thyroidectomy ; it is now rec- ognized that this is due to a general toxemia. As these phenomena were arrested by administering thyroid ex- tract, or by grafting, as long as the physiological action of these remedial agents lasted, it became evident that the thyroid supplied the blood with some substance which in some way de- stroyed the spasmogenic poison, i.e., that the thyroid product was an anti- toxic substance. This is further sus- tained by the facts: 1, that the blood 694 ANIMAL EXTRACTS (SAJOUS). of thyroidectomized animals proved more toxic than that of normal ani- mals, and that it caused convulsions; 2, that the urine of thyroidectomized animals was also more toxic than that of normal animals; 3, that the trans- fusion of blood of the latter into thyroi- dectomized animals counteracted for a time the toxicity of both their blood and urine. These and other facts had shown that the thyroid gland — mainly owing to the parathyroid secretion it contains — is endowed with antitoxic, or, as they have been sometimes termed, "detoxicatory," functions. Yes; it is evidently not only ''toxic substances formed in the metabolism of the body" that the thyroparathyroid secretion proves antitoxic. Charrin, Lindemann, and others have found, for example, that animals succumbed more readily to infections after their thyroid had been removed ; Roger and Garnier, Kashiwamura, and others found that histologically the thyroid showed evi- dences of marked activity, while Torri noted that this was accompanied by an increased production of their colloid substance. Hunt has shown that thy- roid feeding renders white mice much less susceptil)le to poisoning by aceto- nitrile ; Vincent, Frugoni and Grixoni, Leopold-Levi and Rothschild, and oth- ers have observed that thyroid prep- arations combated effectively various infectious diseases, including erysipelas and septicemia. The thyroparathy- roid thus showed itself antagonistic to bacterial toxins and certain other poi- sons, as well as to toxic waste products. This action is accounted for by the fact, pointed out by myself in 1903 ("Internal Secretions," vol. i), that the thyroid secretion is one of the impor- tant agents in general immuiiity — none of the active factors or antibodies of which had been traced to their source. I found, however, that this action was indirect, i.e., that the thyroid secretion or extracts, while a constituent of the l)lood's antitoxin, or alexin, increased the immunizing power of the latter by enhancing the functional activity of the adrenals. This stimulating influence on the adrenals has since been sus- tained by the investigations of Hoskins and others experimentally, wdiile the jiarticipation of the thyroid in the im- munizing process was, four years later, confirmed by the researches of I.. Fas- sin, of the Bacteriological Institute of Liege. Experiments to ascertain the influence of the thyroid gland on innnnnity. The first scries of experiments in a large number of animals (dogs and rabbits) showed that the subcutaneous injection of thyroid product (fluidextract of the fresh gland, the thyroidin of Bur- roughs, \\'ellcome & Co.) is rapidly fol- lowed by an increase of alexin in the serum, a substance discovered by Buch- ner, generally considered as playing an important role in the defense of the body. This increase becomes evident as early as ten minutes after the injec- tion ; it becomes accentuated after one hour, reaches its maximum in twenty- four hours; then the proportion of alexin in the blood recedes more or less rapidly until the normal is reached. The effects of one injection rarely last less than twenty- four hours or more than two or three days. The writer also found that the oral administration of thyroid brought about corresponding effects. To control these results as to their direct relationship with the thyroid, the writer performed complete thyroidec- tomy in 9 animals. One alone, however, survived the operation more than fifteen days, tetany occurring in all, thus show- ing that the parathyroids had been com- pletely removed. In all the operated animals there occurred a marked dimi- nution of the hemolytic and bactericidal alexin, though it never d'sappeared ANIMAL EXTRACTS (SAJOUS). 695 altogether. As the diminution of alex- in might possibly have been due to traumatism, the operative procedures were repeated in fresh animals, leaving the thyroid in situ. But neither the traumatism nor even removal of the spleen caused a reduction of alexin. Louise Fassin (C.-r. de la Soc. de Biol., vol. Ixii, pp. 388, 467, 647, 1907). Further researches on the nature of the process through which the thyroid secretion enhanced the autoprotective power of the blood and of the phago- cytic activity of the migrating and sta- tionary (endotheHal) cells brought me in 1907 to the conclusion that the thy- roid and parathyroid secretions, acting jointly, served to sensitize all phos- phorus-laden cells, normal and patho- logical, and that this thyroparathyroid secretion and Weight's opsonin were "one and the same substance." Among the more direct facts which sustained this opinion were that, while substances capable, as are the opsonins, of sensi- tizing or enhancing the phagocytic ac- tivity of leucocytes had been found in the blood-plasma by Denys and Leclef, Bordet, and others, and Nolf had shown that they were secreted by the red corpuscles, my own observations brought out (1) that the composition of these sensitizing substances was similar to that of the thyroparathyroid secretion, i.e., that they contained io- dine, nucleoproteid, and globulin, and (2) that opsonins, which had been as- similated to Bordet's sensitizing sub- stance by Savtchenko and others, were destroyed at the same temperature as the thyroparathyroid secretion, i.e., at 60° to 65° C. Briefly, besides being endowed with other attributes in com- mon, the sensitizing substances of Denys, Bordet, etc. ; Wright's opsonins, and the thyroparathyroid secretion all proved to be plasmatic products of the red corpuscles, and to show similar chemical properties. Hence my con- clusion that it was as opsonin that the th3^roparathyroid secretion pro- duced its main effects, and the rec- ommendation that thyroparathyroid preparations be used in various in- fections, acute and chronic, to enhance the opsonic power of the blood. My position has been stistained by several investigators. The writer reported the results of experimental and clinical observations which had led him to conclude that the opsonins of the tissue juices and ex- udates were, to a considerable extent, the product of the thyroid gland while simultaneously taking part in the main- tenance of health through its influence on metabolism. He noted elevation of the opsonic index of the serum after injections of thyroid extract into rab- bits. A rabbit treated with L5 c.c. of the extract at two days' interval gave three days after the injection an opsonic index = 2, 4, for example. Another, given the preceding day 1 c.c. of the extract, gave an index of = 3.0. These results, obtained in many animals, and other experiments led the writer also to ascribe the opsonizing action of thy- roid extract to the thyroglobulin of Oswald, which is normally present in the thyroid gland. Stepanoff (C.-r. de la Soc. de bIoI., vol. Ixvi, p. 296, 1909). The writer, having also advanced the opinion that the glands with internal secretion probably play an important role in the phenomena of immunity, undertook to verify this view experi- mentally, as had Stepanoflf, at the Pasteur Institute. The first series of experiments aimed to ascertain the influence of hyperthyroidization on op- sonic variations in the blood of guinea- pigs and rabbits, using mainly the bacilli of tuberculosis, diphtheria, the Bacillus coli, and the staphj^lococcus and streptococcus. A large dose of thyroid (1 Gm. per kilo) was given the first day, but this was reduced daily. In this series, which included 116 examina- 696 ANIMAL EXTRACTS (SAJOUS). tions, the writer states that he always observed that the opsonic power of the blood-serum increased very clearly after thyroid opotherapy. It was, in fact, considerably more than doubled in all but one instance, the exception being that of an animal in which an emulsion of Bacilhis coli only increased the op- sonic power one-half. Might the ingestion of any animal substance by herbivora not have given rise to the increase of opsonic activity? The administration of corresponding quantities of horse flesh to control failed to modify the latter in any way. The writer found, moreover, that the leucocytes of a normal animal when treated ;;/ t'itro with the serum of an hyperthyroided animal showed a dis- tinct increase of i)hagocytic activity. The second series of experiments had for its purpose to ascertain the effects of removal of the thyroid on the op- sonic properties of the blood. The serum obtained from 4 dogs at the time of the characteristic accidents caused by thyroidectomy showed in every instance a most evident diminution of opsonic power. The same experiments con- ducted in the rabbit gave rise to the same results, i.e., he always found a marked decline of opsonic power in thyroidectomized animals. He noted, moreover, that, while traumatism, even a musculocutaneous wound, could cause in a certain measure a reduction of opsonic power, the latter rapidly re- turns to normal, while it maintains itself a very long time at the same level in thyroidectomized animals. S. Marbe (C.-r. de la Soc. de Biol., vol. Ixiv, p. 1058, 1908). Brielly (see the present, 1922, status of the question by R. W. Wilcox, pajfes 688 and 689), the physiological action of thyroid preparations may be summarized as follows: — 1. They enhance oxidation by in- creasing the inflammability of the phos- phorus, which all cells, particularly their nuclei, contain, and by enhancing the functional activity of the adrenals. 2. Their power to enhance the in- flammability of cellular phosphorus ex- tends to ])athogenic elements, bacteria, their toxins or endotoxins, toxic wastes, etc. As such they act as opso- nins, and render these pathogenic ele- ments vulnerable to the immunizing action of the blood and its phagocytes. THE ACTIVE PRINCIPLE OF THYROID.— The thyroid product is an "iodized globulin." As Notkin and also White and Davies hold, the action of the thyroid secretion resembles that of an organized ferment. This finds its explanation in the fact that the thyroidin, to wdiich this applies, is mainly a ferment plus iodine. The identity of this ferment suggests itself when we consider Baumann's analyses of his thyroidin. Among other tests, for example, he found that it was prac- tically insoluble in ether and chloro- form; that it was not destroyed by digestive ferments, and that it stood a temperature of 100° C. These are the specific tests of the oxygen-laden adre- nal product, my adrenoxidase. Again, I found that this substance gave the tests of the plasmatic oxidase; Lepin- ois also found that the thyroid secre- tion contained an oxidase which gave the blue reaction with tincture of guaiac. We have seen, moreover, that adrenoxidase is a globulin : Oswald termed his product "thyroglobulin" and described it as an "iodized glob- ulin." The recent discovery of Kendall of crystalline body in the thyroid, he termed "thyroxin" has already been reviewed on page 693, and its possible role in metabolism described. The crystalline body containing over 60 per cent, of iodine prepared from the thyroid by Kendall, of the Mayo Clinic, was tried on cretins and ANIMAL EXTRACTS (SAJOUS). 597 myxedema patients. The results ments themselves (hemolysis), and justify the view that this substance pv^n tli« fJcc^^- /„. <- 1 • > • . , , . , , s^en tlie tissues (autolysis) proper, is to be regarded as a hormone hav- , , , t^. '^ ing the functions ascribed to the thy- '"^^ ^^ destroyed. Five- or even 4- roid. They very definitely indicated ^ram doses— the former dose of the that a gain, not a loss, of nitrogen is U. S. P. — are never indicated, even in a result of the therapeutic action of the treatment of obesity, thyroid; and vice versa, that a loss of p, 1 j- .1 • , . nitrogen, that is, protein, is due to a ^^ 'oading up the circulation with toxic condition of the gland. They ^^""'^ wastes, these excessive doses may showed also that usually too great an ^^^o give rise to tetanoid movements amount of thyroid is prescribed in and even to true tetany. hypothyroidism. The thyroid of An M-nr^^rf-i^,*- f 4. • xt • 11 -^ , , . ■ « . -^^ important feature in this connec- obesity depends on a toxic effect, as .• , . , it is accompanied by nitrogen loss. *'°"' ^^^^^ver, is that the preparations It should therefore be discouraged. °* desiccated thyroid on the market N. VV. Janney (Arch. Internal Med., vary in strength to a considerable de- xxii, 187, 1918). gree, and that a small dose of a weak PREPARATIONS AND DOSE. P^'^P^^'^tion may prove practically inert —The implantation of a portion of the ^ ^^^''^'^^- ^^^^ '^ ''"^ ^^ the fact that thyroid gland beneath the skin was JT^^ ^'^""^ "^^ ^^ >'^t been standardized, soon superseded by the hypodermic ^^'.^ ^°^^ "°* ^PP^^ to an imported method, but the latter presented an- ^esiccated thyroid, that of Burroughs, other drawback, that of requiring the ^^^^ome and Co., which is standard- constant attendance of the physician. '^^^: ^^"^^ ^'■^'" (representing about 6 Besides this the preparations often f^^'""^ °^ ^h^ ^""^^^ S^^"^) containing produced suppuration. The gland it- ^'^^ °^ '"^^'"^ '" organic combination, self, therefore, administered in the form ^^ '' "P°" ^^'' standard that the dosage of desiccated powder in tablets or cap- '"^commended above is based. It is sules, is preferred by the majority of ^y^ilable in small tablets of 54, r/,, 1, practitioners. This presents also the ^^' ^^' ^"^ ^ grains, advantage of conforming to the Ninth There is also on the market an im- Decennial U. S. Pharmacopoeia {thy- Ported article termed iodotliyrin, sl roideum siccum) made official from mi'k-sugar triturate of the thyroid September 1, 1916. active principle. 1 Gm. of which repre- The average dose recommended in sents 0.0003 Gm. of iodine. The dose the previous Pharmacopoeia was en- ^or adults is given as 10 to 30 grs. (0.6 tirely too large, but this was corrected to 2 Gm.), and is available in tablet in the last edition. It is now 1 3/2 grains form, each containing 5 grains (0.33 (0.1 Gm.). Gm.) of iodothyrin. Its manufactur- But much smaller doses 34 grain and ers claim that, besides possessino- the even less, three times daily may be ad- advantage of definite strength, it is vantageously used, even in the adult, devoid of extraneous matter. It is not While small doses enhance metabolism, regarded as efficacious as the desic- larger doses so stimulate catabolism cated gland. It is a convenient prep- that they cause undue breaking down aration for young children, however of the fats and tissues. owing to the fact that it occurs as a If kept up too long, the blood ele- sweet, whitish powder. 698 ANIMAL EXTRACTS (SAJOUS). When preparations of thyroid gland — which inchide parathyroid — cannot be obtained, a glycerin extract may be prepared by divesting a sheep's gland of fat, and macerating it in an equal quantity in weight of glycerin twenty- four hours. From 2 to 15 minims of the extract may be given daily accord- ing to age. Thyroxin was found to have a defi- nite therapeutic effect in cretinism, improvement in the clinical symp- toms and a gain in nitrogen reten- tion resulting. The optional daily dose was found to be 0.25 mg. (V^fio grain) hormone iodine, representing approximately 0.75 mg. ('/so grain ) thyroxin, and corresponding to 4 grains (0.26 Gm.) of thyroid tablets. It could thus be demonstrated that as a rule too great an amount of thy- roid is prescribed in hypothyroidism. Janney (Arch, of Internal Med., xxii, 187, 1918). UNTOWARD EFFECTS AND THEIR PREVENTION.— The dan- gers attending the use of th3-roid prep- arations depend, to a degree, upon the manner in which the remedy is admin- istered. Beneficial doses, by raising the activity of all metabolic processes, prove tonic, increase the appetite, the strength, and the o.xidations, as shown by a slight rise in temperature. When, however, the dose is too large, a weak, rapid pulse and shortness of breath, vomiting, cardiac oppression, a feeling of tightness around the chest, vertigo, and coma may supervene. Excessive doses have also caused anorexia, diar- rhea, malaise, lassitude, and pain in the extremities ; headache, various eruptions, urticaria, transient and pap- ular erythema and eczema, and, in some cases, nervous manifestations ; neuralgia, delirium, convulsions, delir- ium of persecution, aphasia, monople- gia, etc. When dried powder or com- pressed tablets that are not fresh are used, symptoms of ptomaine poisoning tnay be added to those mentioned. Hence, the observations that these prep- arations are more likely to produce such effects during the warm weather. The best guide is the pulse. Any considerable quickening or palpitation should lead us to discontinue the drug until the cardiac action is again normal. There are no dangers in the use of the drug, provided we begin with small doses, from M to 1 grain, and grad- ually increase, watching the pulse. It should never be given to a patient who cannot be closely watched. In some cases, although no other un- toward symptom appears, the patient loses flesh. This is apt to occur when 2 grains of the dried gland three times daily in the adult is exceeded. Chronic poisoning, characterized by rapid pulse, emaciation, weakness of the limbs, general debility, and mydria- sis have also been observed in individ- uals who had undertaken, without med- ical advice, to treat their corpulency, and who had, therefore, subjected themselves to excessive doses. TREATMENT OF THYROID POISONING.— As a rule, cessation of the use of thyroid preparations ar- rests the untoward effects. When such is not the case, however, arsenic, as shown by Mabille, antagonizes the toxic phenomena. Fowler's solution, from 3y2 to 5 drops three times daily, suffices in most instances to arrest all morbid effects. Mabille's observation that arsenic ob- viates the unpleasant symptoms excited by thyroid preparations were confirmed by Evvald. In 5 cases of idiopathic goiter, in 1 case of obesity, and 1 of infantile myxedema, iodothyrin was given in pro- gressive doses of from 3% to 30 or 38'/$ grains daily. At the same time arsenic ANIMAL EXTRACTS (SAJOUS). 699 was given, either in pills or as Fowler's solution, in doses increasing proportion- ately to the iodothyrin of %4 to Ko or even Is grain daily. Although the 7 cases took respectively 231. Ill, 86. 320. 108, 296, and 125 iodo- thyrin tabloids, containing nearly 4 grains each, beyond occasional increased fre- quency of the pulse no symptoms of thy- roidism appeared, so that the course could be continued uninterruptedly. Arsenic, therefore, appears to suppress thyroidism with greater certainty than atropine does iodism. and it is possible to give iodothy- rin safely in doses and for a period capable of producing delinite therapeutic effects. The addition of a cardiac tonic, preferably adonidin, to thyroid is recommended whenever the latter preparation is to be used for any length of time. The following for- mula is employed: — B Sodium cacodylatc %oo gr. Adonidin ^/'3o gr. Thyroid gland (dry f^ozcdcr). 1 gr. For 1 compressed tablet. When fresh adonidin cannot be obtained (its price is exceedingly high), caffeine may be substituted in doses of % grain. Thyroid therapy will receive a new stimulus as soon as the medical profession appreciates the fact that the addition to the thyroid of proper amounts of arsenic and a cardiac remedy will render the medication more efficient and deprive it of all or nearly all its deleterious effects. Tleinrich Stern (American Medicine, Jan., 1910). THERAPEUTICS.— The many disorders in which thyroid prepara- tions have been recommended ("nearly all the chronic and many of the acute troubles known to humanity," as one author remarks) have naturally in- spired considerable mistrust as to their actual therapeutic value. Gradually, as the harmfulness of large doses as- serted itself and the physiological role of the thyroparathyroid apparatus be- came unraveled, however, their indi- cations became better defined. It may now be said that in sharp con- trast with the empirical methods of the past thyroid preparations, when employed intelligently, are of great value in many disorders, both acute and chronic, mainly through their po- tent influence over metabolism due to the contained organic iodine. Recent experimental and clinical investigations have well shown that the thyroid acts more powerfully in accelerating metab- olism than any other known agency. The writer's experiments empha- size the extraordinary affinity of the thyroid tissue for iodine. As high as 18.5 per cent, of a given intake of iodine by mouth may be recovered from a thyroid whose ratio to the body weight is as 1:687. Again, maximum thyroid effects may be in- duced by minimum amounts of iodine. The amount of a given in- take absorbed depends, for the most part, on the size of gland and the existing degree of hj^perplasia or the degree of saturation with iodine at the time of its administration. Marine (Jour. Biol. Chem., Oct., 1915). Basal Metabolism. — This method of ascertaining the degree of activity of the thyroid gland has recently received considerable experimental and clinical support. As it is reviewed under Graves's disease, it may be recalled that while the basal metabolism of a normal in- dividual varies but about 10 per cent., anv oreater variation is of endocrine origin, the thyroid furnishing the widest variations. The writer found in a case of ex- ophthalmic goiter that the standard of metabolism reached 80 per cent, above normal, and in a myxedema patient 40 per cent, below normal. Krogh (Ugeskrift f. Laeger, Dec. 29, 1916). 700 ANIMAL EXTRACTS (SAJOUS). In the light of the functions attrib- uted to the thyroid secretion in the foregoing pages, it governs tissue me- taboHsm by rendering all phosphorus- laden cells susceptible to oxidation. When, therefore, the thyroid principle is deficient in the body, both phases of metabolism — including,of course, that of carbohydrates — the building up and the breaking down of tissues, are correspondingly inhibited. The most exaggerated expressions of this condi- tion are, as is well known, the syn- dromes known as myxedema and cre- tinism. The characteristic symptoms of these disorders exemplify clearly deficient metabolic* activity and its ■consequences. In m^^xedema we have, among other symptoms, for example, the low temperature, 95.5° F. in some instances, both in the mouth and rec- tum; great sensitiveness to cold, reduction of the urea output — some- times to 50 per cent, of the normal — cyanosis of the lips, cars, and extrem- ities on exposure to slight cold,, and many secondary results of deli- cient metabolic activity, anemia with marked pallor, general relaxation of the arteries, muscular weakness, mental torpor and vertigo, and the cu- taneous anesthesia. In the cretin, we have, besides, all the phenomena of ar- rested development, both physical and mental, as shown by the dwarfed body and the idiocy. Hypothyroidia, or Hypothyroid- ism.— This is a condition akin to the above, but much less marked, fre- quently met in practice. The thyroid apparatus supplies a part only of that required by the tissues, and the result- ing phenomena recall closely some of those observed both in myxedema and cretinism : chilliness and subnormal temperature, coldness of the extremi- ties and sensitiveness to cold ; fatigue on slight exertion ; constipation with tendency to tenesmus; frequent at- tacks of migraine, "sick headaches" with nausea, vomiting, etc., and other periodic manifestations of autointox- ication— due to inadequate reduction of waste products and their retention in the blood. The skin taking part in the process of elimination, urticaria and eczema are frequently observed, while transitory edemas of the brow, around the eyes, and sometimes of the face, even in the absence of albumi- nuria or casts, point to renal fatigue. Enuresis is commonly observed in children of this type and may persist to adult age. The patient is subject to frequent catarrhal disorders of the re- spiratory passages, usually ascribed to colds, but due mainly to vascular and glandular relaxation. A tendency to early alopecia, including the eyebrows (especially the outer third), is also noticeable — a sign of deficient general nutrition which coincides with a marked proclivity to early senility. In women the menstruation appears late, owing to retarded development, and there is a proclivity to metrorrha- gia due to laxity of the muscular coats of the uterine arterioles, while pelvic disorders are apt to occur owing to de- ficient support of the uterus, lack of tone in its muscular elements. Leucor- rhea is also frequent, owing to relaxa- tion of the glandular elements of the whole genital tract. Such women con- ceive readily, but abortion is very fre- quent among them ; if the fetus is carried to the normal period, they have little or no milk. Children born of such mothers make up the largest number, if not all. the cases of cretin- ism, rickets, harelip, cleft palate, and other malformations usually ascribed ANIMAL EXTRACTS (SAJOUS). 701 to hereditary influence. We are deal- ing simply with deficiency of the iodine in organic combination which the thyroparathyroid glands supply to the organism to sustain their intrinsic metabolism, i.e., their vital activity. Hertoghe has urged the importance of the maternal thyroid on the develop- ment of the fetus, hypothyroidia from fault be added tuberculosis, hereditary syphilis, alcoholism, inanition, saturn- ism, or diabetes, the child will show un- doubted signs of these taints, and will probably be a myxedematous cretin, with signs of rickets and achondro- plasia, and to this cause may be assigned such malformations as harelip, cleft palate, bony deformities, hypospadias, or undescended testicle. Should the maternal taint be but slight, the child Adipositas (8 months old). Weighs 36 pounds. (Sheffield.) any cause favoring cretinism in the child. It also promotes sterility, the use of thyroid gland being often fol- lowed by pregnancy. Hypothyroidia is often the cause of obesity in children, as well as in adults (see annexed cuts), and of the cold feet and hands and other phenomena observed in fat, pasty children. If the mother has at her disposal suf- ficient store of thyroid secretion, the child does well; but if there is thyroid insufficiency, and especially if to this will merely be very backward, which is a matter of small amount in boys, and if after a time righted by the thyroid equilibrium being established ; but in girls menstruation is late in being estab- lished; uterine retroflexion is frequent; the chest is undeveloped. The author has often seen women Hearing 40 years of age who are fat and whose menstrual flow is excessive take thyroid extract in order to reduce their obesity. He has often seen the menstrual flow in these women become modified, their stoutness decrease, and the women find themselves pregnant, 702 ANIMAL EXTRACTS (SAJOUS). when they had for a long time given up all hope of ever being so again. He has often by means of thyroid -extract brought to a successful end a preg- nancy in v^^omen who have repeatedly miscarried. It is often noticed that in adults incontinence of the urine can be stopped by rest in bed. This comes about from the fact that, while resting in bed, the patient is subject- artificial feeding, these signs become more pronounced, with eczema, urti- caria, tardy dentition, etc. It seems evi- dent that nurslings receive in mother's milk some of the products of the mother's thyroid functioning. The physiological hypothyroidism of the new- born may assume pathological propor- tions ; any derangement in thyroid functioning on the part of the mother Adipositas. Same case, back view. {Shtffield. ) ing his tissues to large doses of thy- roid secretion. In the case of a pregnant woman the increase of thyroid secretion often becomes excess- ive during the pregnancy, and the woman suffers from the symptoms of excessive thyroid secretion. Hertoghe (Bull, dc I'Acad. Roy ale de Med. Bel- gique, April 27, 1907). Thyroid insufficiency is the cause of many of the ])]ienomcna noted in young infants, such as a tendency to obesity, to transient edema, cold feet and hands, scanty and brittle hair, vasomotor dis- turbances, vomiting, somnolency, and slight resistance to infections. With or wet-nurse may lead to severe symp- toms of hypothyroidism in the infant. In several instances in the writer's experience infants became my.xedema- tous when the mothers had goiter. In other cases, the healthy infants of healthy parents became myxedematous when they had a wet-nurse with goiter. All these children were cured with thyroid treatment and change of nurse. Experimental research with goats has confirmed the actual occurrence of transmission of th5'roid secretion bj' the placenta and in the milk. Concetti (Annales de med. et chir. infantiles, Aug. 15, 1909). ANIMAL EXTRACTS (SAJOUS). 703 The rudimentary forms of myx- edema or hypothyroidism in children are particularly liable to escape recog- nition, while thyroid treatment in time is almost a certain cure. In a case of this kind a boy of 6 had not grown in the last two years, but seemed otherwise normal, although not particularly bright. Under cau- tious thyroid treatment by the end of eighteen months he had grown 11 cm., nearly 4^/2 inches. In 2 other cases the myxedema developed after severe measles or mumps, with acute thyroiditis in the latter case. The thyroid treatment ordered was soon abandoned by the family, and the child developed pronounced myx- edema, but after two years it spon- taneously subsided. In a fourth case the myxedema developed after a severe fall over a balustrade, the throat in front bleeding from the in- jury. Thyroid treatment promptly cured the child. "Pasty" children, fat, pale, and flabby, may be suffering from hypothj'roidism and require thy- roid treatment. Stoeltzner (Jahr- buch fiir Kinderheilkunde, Aug., 1910). Thyroid insufificiency often under- lies irregular, delayed, and erratic dentition and decayed teeth in chil- dren. Administration of thyroid is markedly effective especially in de- layed dentition and children border- ing on cretinism. The writer in- variably starts to regulate the teeth of a young child by giving thyroid. M. C. Smith (Boston Med. and Surg. Jour., Oct. 19 and Nov. 9, 1916). The writer found that in some cases of hypothyroidia, in which the administration of animal thyroid preparations only partially controlled the symptoms, they were almost completely relieved by human thy- roid extracts. S. P. Beebe (N. Y. Med. Jour., civ, 445, 1916). Hypothyroidia, in so far as nutri- tion is concerned, may be defined, therefore, as that condition of the body in which, owing to deficient production of the thyroparathyroid secretion, cel- hilar metabohsm is slowed sufficiently to inhibit more or less all functions. Hence, the value of thyroid prepara- tions in infantile marasmus. In infantile wasting the writer gives thyroid in a diluted milk and cream mixture with sodium citrate, 1 or 2 grains to the ounce of milk. In a day or two cream is gradually added, ■/' a teaspoonful to the feeding bottle. Out of 80 cases thus treated 72 were infants under 9 months and their his- tor}' was simply one of wasting. The other 8 had a wasting supervening on some acute diseases; 63 cases did well; 5 cases presented syphilitic histories in which wasting was a marked sj^mptom. Mercurj' was first given and later thyroid. Three immediately gained and eventually recovered. In older children the re- sults have also been favorable, ex- cept when tuberculosis was present. In children under 9 months, the author began with I3 grain of dried thyroid once daily. Larger doses often seemed to induce a diarrhea. In the giving of thyroid it is advis- able to test the stools frequently to see whether they are acid or alkaline. In case acidity is found the bicar- bonate of soda may be given three times daily, and when the natural alkalinity of the stools is restored the thyroid will begin to e.xert its bene- ficial results. No grave symptoms followed the thyroid therapy. In 6 cases a punctiform rash appeared, confined in 2 cases to the front of the chest. It was evanescent and disappeared without treatment in the course of twelve to twent3'-four hours. In only 1 case was it neces- sary to stop the thyroid (three days) in order to cause the rash to dis- appear. J. W. Simpson (Brit. Med. Jour.. April 30. 1910). Its administration to mothers who have not enough milk for their babies has, in the writer's practice, with one exception, been followed by an in- crease in the flow, making it possible to get along without artificial feed- 704 ANIMAL EXTRACTS (SAJOUS). ing where such feeding had been necessary with former children and would have been necessary in these cases, as shown by decreased flow whenever the thyroid was withheld. E. W. Demaree (Western Med. Rev., May, 1910). The symptoms of typical hypothy- roidism, l)esides the adiposis, are scanty or absent menstruation, drow- siness, slow pulse, dry skin, local pufifiness and perhaps slow mentality. The writer cautions against the care- less use of thyroid. It should be added to the list of poisons and never sold unless with physician's prescrip- tion. It is potent for harm, and a little too much may push a wavering thyroid gland to hypothyroidism. O. T. Osborne (Jour. Amer. Med. As- soc, Nov. 2, 1912). The writer met with a case of double pneumonia and pleural collec- tion which was followed by the fol- lowing clinical syndrome: intense abdominal pain, constipation and slight meteorism, profuse sudation, normal temperature and a slow, ir- regular pulse. At autopsy the writer found a hemorrhage in both supra- renals; the medullary substance was entirely destroyed in 1, and greatly in- volved in the other. The cortex of the glands was preserved. The writer points out the concordance between the clinical signs offered and the physiological data known, which show that the disturbances arising in this case resulted from a lack of tonus of the sympathetic, that is to say, from an adrenalin insufficiency. Low- enthal (Berl. med. Woch., Nov. 25, 1918). In contrast with this condition, and exemphfying clearly what we are to expect from thyroid preparations, is the opposite condition — hyperthyroidia. Hyperthyroidia, or Hyperthyroid- ism.— The opinion of Mobius that ex- ophthalmic goiter or Graves's disease is due to overactivity of the thyroid (treated in full in the fifth volume) has steadily gained ground. But this imposes the necessity of establishing clearly the diagnosis of this disease, for there are many disorders that are due to thyroid overactivity, the so- called "larval" or "aberrant" types, the "formes frustes" of the French, or "pseudo-Graves's" disease, which should not be confounded at all with true exophthalmic goiter, since the ac- tive or erethic stage of the latter is aggravated by the use of thyroid prep- arations, while the "pseudoforms" are benefited by these agents. This does not, however, militate against the fact that exophthalmic goiter and all the above-mentioned subtypes are expres- sions of thyroid overactivity, or hyper- thyroidism. In all we meet, more or less defined — in proportion with excess of thyroid secretion produced — the same group of phenomena, all of which can readily be explained by excessive tissue metabolism and its consequences. Tests.— Loewi in 1908 found that the instillation of 1: 1000 solution of adrenalin in the conjunctiva produced dilatation of the pupil with abnormal readiness when hyperthyroidia was present owing to the increased irritability of the dilator fibers of the iris due to the disease. Numerous observers have confirined these observa- tions. The best adrenalin test is that of E. Goetsch (N. Y. State Jour, of Med., July, 1918) based on the fact that a patient suf- fering from hyperthyroidism is hypersen- sitive to adrenalin. A hypodermic syringe with a fine needle is used to inject 0.5 c.c. (8 minims) of the 1: 1000 solution of ad- renalin into the deltoid region subcutane- ously. The positive reaction is character- ized by an early rise of blood-pressure and pulse varying from 10 to SO and normally proportional to the degree of thyroid in- toxication present. There occur also the symptoms, such as asthenia, tremor, throb- bing, vasomotor changes, apprehension and nervousness, which characterize a mild case, or an increase of previous symptoms. ANIMAL EXTRACTS (SAJOUS). 705 Lymphocj'tosis indicates a patho- logical state due to toxic influences from the thyroid. It is a symptom that cannot be simulated, and has often proved of decisive value in dis- tinguishing between functional or organic heart disease. Instillation of epinephrin in the eye also causes mydriasis that is prompt, marked and lasting for several hours, when the thyroid is functioning abnormally. Curschmann (Med. Klinik, Mar. 5, 1916). During the great war, many cases of hyperthyroidism were observed among the troops, due to the intense stress, and exertion to which they were sub- jected. Hyperthyroidism is seen very fre- quently in the military service age, the young and middle aged adults. Owing to its symptoms, it interferes with a soldier's duties; it is of great importance to diagnose this condi- tion, and, if it exists, to what degree. This can be accomplished by means of galvanopalpation in which a posi- tive diagnosis can be made when gal- vanohyperesthesia and a high degree of reaction of the blood-vessels is ob- tained. Max Kahane (Wiener klin. Woch., Feb. 11. 1915). The most striking feature of cases of hyperthyroidia in the recruit in nearly every instance is tachycardia. This is the sign because of which most of the cases report to the regi- inental medical officer or on which they apply for exemption or dis- charge. It is constant in practically all examples of the syndrome, though it varies very greatly in degree. It is present alike in recruits presenting themselves for initial examination, in those who report later, and after con- siderable drill and army routine may have further served to upset the men- tal, emotional and circulatory equi- librium of these patients. The tachycardia is ' rarely accom- panied by arrhythmia even in cases of very marked degree, and polygraphic studies, except in instances compli- cated by other vascular conditions, show, aside from rapidity, few signs of abnormal action, except that in the same case there is under varying con- ditions usually great variation in the rate of systoles. Practically always the rate is increased by exercise, though there are exceptional cases in which, as in ordinary palpitation, ex- ercise may slow the rate, especially when the attention is thereby dis- tracted; but speed of action is even more constantly accelerated by ex- citement and disturbing emotional factors. Closely associated with tachycardia is an obvious and subjective throb- bing of the superficial vessels, notably of the carotids, of the brachials and even of the femorals, while that of the aortic, in moderately thin persons, is also quite evident. Harlow Brooks (Amer. Jour. Med. Sci., Nov., 1918). The thyroid was found enlarged in about two-thirds of recruits exam- ined in whom tachycardia existed, sufficiently in some to constitute true goiter and to produce pres- sure dyspnea. In most of these an ancestral history of goiter, particu- larly on the maternal side, was given. Exophthalmos was present in cases of long standing, sufficiently so, in some instances, to have produced conjunctival hyperemia and desicca- tion. In some, the exophthalmos had developed suddenly. Virtually all pa- tients were rapid and large eaters, but they bore acute infections badly, while tobacco produced in them more serious symptoms than in the average smoker. This symptom, which includes all the cardinal signs of Graves', was observed chiefly among men belong- ing to nationalities in which the emo- tional element is common: the Hebrews, Italians, and Irish, the fre- quency following the. order named. The negroes, least of all races, showed a predilection to the dis- order. In civil life emotional stress of any kind, fright particularly in the course of accidents accompanied by trau- matisms or blows, car or train dis- 1—45 706 ANIMAL EXTRACTS (SAJOUS). asters, mental distress, worry, violent emotions, etc., are familiar causes of Graves' disease. A personal case due to an accident and rapidly proceed- ing to recovery under medical treat- ment, recurred at once after a second accident, though the patient had suf- fered no traumatism. C. E. de M. Sajous (Penna. Med. Jour., Jan., 1919). Untoward Effects. — When large or excessive doses of thyroid preparations are administered, there occurs: a rise of temperature, a feehng of abnormal warmth ; tachycardia due to excessive excitability of the heart muscle; pains, trembling owing to a similar condition of all muscles; sweating due to over- activity of the sweat glands ; vomiting and diarrhea owing to abnormal irri- tability of their gastric and intestinal neuromuscular supply. Excessive me- tabolism involving the production of a surplus of wastes, the kidneys are overburdened and overactive, and the cutaneous emunctories likewise, the lat- ter causing pruritus and a papular eruption, beginning, as a rule, over the scapulre. As in Graves's disease, hyper- thyroidism and excessive doses of thy- roid may produce apparent protrusion of the eyeballs, the palpebral muscles being retracted owing to their abnormal contractility and changes in carbohy- drate metabolism. In a study of 27 cases of hyperthy- roidism, excess of sugar in the blood was found to be a very common ac- companiment of the latter condition, occurring in 90 per cent, of instances in the moderate and severe types of cases. Glycosuria, either spontaneous or alimentary (100 Gm. of glucose having been given), was an equally constant symptom.. Alimentary hy- perglycemia and glycosuria were even found not uncommonly in the very mild cases. Marked diagnostic sig- nificance is attached to the lowered carbohydrate tolerance in hyperthy- roidism, its presence being highly suggestive where alcoholism, fever, asphyxia, neurasthenia, and the vari- ous other ductless gland disorders can be excluded. H. Rawle Geyelin (Arch, of Internal Med.. Dec, 1915). The writer describes cases in which the condition of hyperthyroidism was the cause of the carbohydrate toler- ance being destroyed. His first case presented the classical symptoms of the 2 diseases, diabetes mellitus and exophthalmic goiter. Not suspecting that the glycosuria might be related to the coexisting Graves's disease, the latter was regarded as the lesser of the two evils and treatment directed entirel}' toward the former. A total restriction of carbohydrates was un- availing in securing sugar-free urine. While the percentage was reduced, the sugar content of the blood re- mained unchanged. The patient fin- ally died in coma. Before the second patient with the same syndrome was encountered, the author having acquired some experi- ence with the boiling water injec- tions of Porter, applied this method to his second case together with the usual dietary treatment of diabetes. The goiter was injected daily, about 60 minims (3.75 c.c.) of boiling water being used. In 4 days a carbohydrate tolerance was gained, increasing with each succeeding injection till, finally, with extirpation of the goiter, normal tolerance was completely restored. Reference is made to the work of Sainton and Gastaud of Paris, and the statistics given by them show the frequency of diabetes in exophthalmic goiter as 3 in 100 cases. Clinically, diabetes occurring in the course of Graves's disease is manifest in two ways: (1) as a temporary or slight glycosuria with the usual symptoms of diabetes only present in a trifling degree. (2) as a well-established con- dition, with all the characteristic symptoms present, the latter fre- quently even dominating the clinical picture as a whole. The possibility of the adrenals participating in such ANIMAL EXTRACTS (SAJOUS). 707 a glj'cosuria is considered, owing to the thyroido-adrenal origin of exoph- thalmic goiter as taught by the Vienna school. This teaching is based on the theory that a relation exists between the thyroid, pancreas, and chromaffin system. J. C. O'Day (Surg., Gynec. and Obstet., Feb., 1916). A case of thyroidism in an infant from administration of thyroid extract to the mother, a woman aged 34 who had ex- ophthalmic goiter, was observed by Bram- well. On December 24th thyroid extract (two 5-grain tabloids daily) was adminis- tered to the mother. On January 1st the child had been sweating profusely for sev- eral nights. It w-as looking ill and was sleepless. It had vomited every morning for three days. The extract was conse- quently stopped for five days. The child immediately improved, and on January 4th was quite well. On the 9th, thyroid extract was again given to the mother. The next day the child vomited, was again restless, did not look w^ell, and sweated profusely, etc. The child was weaned and after this remained perfectly well. The administration of thyroid gland substance, or thyroid extract, is capable, if given in sufficient amount, of inducing a toxic state which in al- most every essential is similar to Graves's disease. An artificial state of hyperthyroidism is thereby pro- duced, which duplicates almost in full the morbid syndrome. Even the characteristic exophthalmic symp- toms have been observed after thy- roid feeding by Auld, Beclere, and others, and Edmunds was able to in- duce proptosis, widening of the pal- pebral fissure, and dilatation of the pupils in six monkeys by this means, even after excision of a portion of the cervical sympathetic. A. R. Elliott (Amer. Jour. Med. Sci., Sept., 1907). To determine the relation between the thyroid and the reproductive life of women, the writers studied 1000 cases, 550 being primiparse and 450 multiparse. In these 97 cases of en- larged thyroid were found, i.e., in 64 primiparae and in 33 multiparse. A family history of goiter was present in 8 cases (7 primiparse, 1 multipara). In 6 primiparje there was a history of menstrual disturbance. Hyperthy- roidism was present in varying de- grees in 7 cases and probably in 1 other case, although there was no palpable thyroid in this case. Of the whole series of thyroid enlargements 20 cases had already been known to have some degree of goiter before pregnancy; 30 cases developed during the pregnancy; while 47 cases were doubtful. Markoe and Wing (Bull. Lying-in Hosp. of City of N. Y., Nov., 1912). Referring to juvenile hyperthy- roidia, the writer states that in a period of 8 years there have been 1512 patients operated upon at the Mayo clinic for exophthalmic goiter. Of these but 5 were under 10 years of age. In each there was a firm, noticeably enlarged thyroid appar- ently hyperplastic to the touch. The following symptoms were noted: vasomotor disturbance of the skin in 1, tremor in 3, mental irritability in 4, tachycardia in 5, exophthalmos in 5. All the other features observed in the disease in adults participate in the vigorous activities of their asso- ciates without apparent cardiac or muscular distress, while none of them even approached the crisis so fre- quently seen in adults. W. H. Lewis (St. Paul Med. Jour., Feb., 1914). The writer found signs of exces- sive or perverted functioning of the thyroid as the main disturbance in 66 of his first 600 patients in the Posen military hospital; in 420 others it formed part of the clinical picture. In the 66 cases of actual thyrosis, 11 presented gastro-intestinal symptoms as the principal disturbance and these were manifest also in 64 of the group of 420. Thus gastro-intestinal disturbance was evident in one-sixth or one-seventh of all the cases. It was mainly in the form of gastral- gia, loss of appetite, eructations and sometimes a tendency to vomit. In 34 of the group of 66 there was an unmistakable tendency to goiter, and 708 ANIMAL EXTRACTS (SAJOUS). in 254 of the group of 420 mentioned above the thyroid could be palpated. Among the total 486 men with thy- roid symptoms signs of an apical process were found, probably of tuberculous origin, in 210 cases. The writer warns expressly against iodine when there is a possible tendency to thyrosis. Caro (Deut. med. Woch., Aug. 19. 1915). Irritable heart, now so prevalent among troops, is almost invariably associated with hyperthyroidism. The X-ray is the most satisfactory method of treatment. The thyroid gland should be exposed to a full Sabouraud dose filtered through 1 or 2 mm. of aluminum each week until the desired degree of destruction and reduction in activity has been at- tained. Along with this treatment there should be the usual enforced rest and building up process. The usual period required for restoration to health is about 2 months. F. A. Stoney (Lancet, Apr. 8, 1916). With the pathogenesis of these two syndromes clearly defined, the various disorders in which thyroid prepara- tions are indicated suggest themselves. viz., those in which any of the signs of /73'/>othyroidi.^m are more or less dis- cernible. The pathogenesis of hyper- thyroidism being also apprehended, the limitations of thyroid treatment also appear: the doses utilized should be adjusted in each case to the degree of hypothyroidism that is present. The medical treatment of hyper- thyroidism, to be successful, requires a careful study of each patient. A simple diagnosis followed by the more or less perfunctory injection of antithyroid serum will in a small percentage of cases be followed by favorable relief, but to restore the patient to complete good health re- quires a careful analysis of the con- ditions in each individual. The degree to which each individual patient is subjected to these measures is a mat- ter that can be determined only by the individual conditions in each case. 1. Rest; physical, mental, emotional. 2. Diet; rigid meat-free diet, and ex- clusion of all forms of stimulation, such as tea, cofifee, and alcoholics. 3. Administration of antithyroid serum. 4. Clearing up of all chronic affec- tions. 5. Maintenance of hygienic conditions of the intestinal tract. 6. The judicious administration of small doses of iodine, always in the form of potassium iodide. This agent is not indicated in all cases, and is used only when the intense activity has been controlled. 7. The proper use at the right period of the treatment of suitable doses of X-ray. 8. The administration of neutral hydrobro- mide of quinine in a small percentage of patients during the later periods of treatment. Hyperthyroidism is not exclusively a surgical condition, although enthus- iastic surgeons so classify it. The operated patient is by no means well and needs long continued medical treatment to make a complete recov- ery. Beebe (Interstate Med. Jour., Feb., 1918). Cretinism. — This condition repre- sents the extreme type of hypothyroid- ism in the young. The value of thyroid gland is such in this distressing disor- der that it may be regarded as a specific — the only agent, in fact, which influ- ences it at all. The earlier it is used, however, the better the results; hence, the importance of early signs of the dis- ease, the most prominent of which are in infants (see article on "Cretinism"), enlargement of the tongue and of the thyroid, myxedematous swelling, arrest of growth, delay in learning to speak and walk, relative deficiency of intelli- gence, dryness and scaliness of the skin, scantiness of the eyebrows and eye- lashes, puffiness of the lids, and facies of old age. The enlargement of the tongue and of the thyroid are the most positive signs of cretinism in the infant. The ANIMAL EXTRACTS (SAJOUS). 709 shape of the nose and the complexion are not characteristic at this early stage, and the myxedematous swell- ings are not observed until after the end of the first year. Early diagnosis of acquired cretinism is still more difficult. Backwardness in learning to walk and talk is the most reliable sign. In the endemic regions the parents are now being educated to watch for the early signs. Von nitrogenous foods being more perfectly assimilated, the nitrogen excretion rises — sometimes beyond that ing"ested. There is loss of weight owing to ab- sorption and excretion of the excess of fluids in the tissues — an efifect accom- panied by marked thirst — in some cases, as observed by Marie, and in- creased activity of the kidneys. The Case of cretinism. Result of four months' treatment. Growth, 4 inches. Intellect approaching normal. (Moore.) Jauregg (Wien. klin. Woch., Jan. 10, 1906). A comparison of the metabolic ac- tivity between a cretin over 3^^ years old and two normal infants 83^2 months and 10 months old, showed that it was 25 per cent, lower in the cretin than in the two infants. Talbot (Amer. Jour. Dis. of Child., vol. xii, p. 145, 1916). Soon, sometimes within a few days, the effects of whatever preparation is used begin to appear: the appetite in- creases, the temperature rises, and, red corpuscles and hemoglobin are simultaneously increased. The wrinkles and edema disappear; the harsh, dry skin becomes soft, smooth, and moist; the hair from coarse and thin becomes thick and fine. Growth is resumed, and proceeds with great rapidity in children, sometimes at the rate of one inch per month. They do not, as a rule, however, grow tall. The brain responds more slowly, but considerable intelligence is gained in most instances, at times even that of 710 ANIMAL EXTRACTS (SAJOUS). an average child. The later in life cretinism develops, the better are the chances of improvement in this direc- tion ; occasionally none is observed. In other particulars, all degrees of cretin- ism, especially in sporadic cases, may be said to be improved, the best results being obtained in young children. Series of nearly 100 cases in which three years and more have passed since treatment was commenced. All degrees of cretinism and all ages were u;imistakaldy bcnelited by the treatment, but the Iiest results were obtained with the younger children. Complete cure was the rule in the milder cases, without serious impair- ment of the hearing, when treatment was begun in early infancy (at 6 weeks in 1 case). Von Jauregg (Wien. klin. Woch., Jan. 10. 1906). Since 1905. the Austrian govern- ment has been supplying thyroid tali- lets free of charge in seven endemic foci of cretinism with medical inspec- tion twice a year. About 108,600 tab- lets were thus distributed in 1907. and 157.900 in 190S: the number of per- sons taking them was 1011. and 608 were still under the th^'roid treat- ment at the close of 1908. The re- sults are tabulated under various headings, special attention being paid to the increase in height as the most certain index of the benefit derived. Other findings are more liable to be influenced by subjective impressions. The report states that the results have been extremely satisfactory, confirming the efficacy of thyroid treatment as a prophylactic measure, especially in endemic foci of cretin- ism. In 677 cases followed to date marked improvement was obtained in 48.6 per cent., and only 8.6 per cent, showed no benefit from the course. The most striking proof of the bene- ficial influence of thj'roid treatment on the growth is the fact that in 377. that is, 85.7 per cent, of all cases, the former dwarf cretin children grew to be taller than the normal standard for their age. As a rule, treatment was restricted to school children: the oldest cretin was 26 years old. Even after 20 a number of the cretins grew much taller and the other symp- toms of cretinism became attenuated. This growth at this age is so sur- prising that it seems as if the grow- ing power of the preceding years had been held in reserve, until suddenly released by the thyroid treatment, when it made all its force felt in a relatively short period. A large number of the more interesting cases are cited in de- tail. One cretin, 20 years old, grew 11 cm., but then refused to continue treat- ment, as he outgrew his clothes too fast. He did not lose his milk teeth until after thyroid treatment was commenced, although those of the second dentition were in place. A. von Kutschera (Wiener klin. Woch., June 3, 1909; Jour. Amer. Med. As- soc, July 17, 1909). Case of cretinism in a child of 4 years which looked still like a 10 months' babe. No traces of the thy- roid, could be discovered on palpa- tion. Thyroid treatment was then commenced, in 3 months the child had grown 10 cm. in height, and has developed normally since, and is now lively and healthy. C. Doderlein (Norsk Mag. f. Laegevidenskaben, July. 1910). The writer observed a case of com- plete cretinism in which normal men- tality recurred in a girl Sj/2 years of age, who had first come under his observation when she was 3^4 months old. At that time she had all the typical characteristics of cretinism. Her extremities were the shortest he had ever seen. Her head was cov- ered with a thick mass of coarse, flaxen hair, her nose showed no de- velopment, her tongue protruded, her skin was dry, and her flesh showed no resiliency. She showed no anima- tion, even hunger apparently forming no part of her desires. -At the pres- ent time she stood 40 inches in her shoes and she weighed 43 pounds 5 weeks ago, which was more than the norma! weight and height of the average child of her age. There was ANIMAL EXTRACTS (SAJOUS). 711 apparently nothing abnormal in the condition of the child at the present time; she plaj'ed and talked just as any other child. The absence of the thyroid could not be attributed to been given twice daily. This amount was gradually increased until for a time, when she was about 4 years of age, she took 5 grains {0.3 Gm.) daily. Under this amount she de- Thyroid extract in cretinism. Cretinic idiot, 7 years old when thyroid treatment was begun. Had ceased to develop when 3 years old. Changes after one year's treatment. Growth Bli inches. (J. B. McGee: Cleveland Medical Gazette, December, 1900.) trauma, since there was nothing ab- normal at the time of birth except that the labor was rather precipitate. Thyroid medication was begun at the time he first saw the child, % grain (0.016 c.c.) of thyroid extract having veloped the typical signs of excess of thyroid. For some months she had been getting 3 grains (0.2 Gm.) daily. Very soon after beginning the thyroid treatment her hair came out in great masses and her skin came off 712 ANIMAL EXTRACTS (SAJOUS). in sheets, 2 or 3 inches coming off in 1 piece, and the child was practic- ally made over in a few weeks. The writer thought she was worth while presenting as demonstrating the re- sult of thyroid medication together with persistent and careful attention on the part of the mother. The case showed that if one took a case 100 per cent, cretin early and adminis- tered the amount of thyroid that nature intended the child to have, one could get a perfect recovery, pro- vided the child had no other defect in any other ductless gland secretion. W. B. Iloag (Med. Rec, Apr. 22, 1916). To obtain such results, however, it is important to distinguish true cretins from idiotic dwarfs in whom thyroid is less beneficial or of no benefit what- ever. These are the mong'ol or kal- muck idiots and the micromelic or achondroplasic dwarfs. A comparison of the metabolic ac- tivity between a cretin over 3M years old and 2 normal infants 85/2 and 10 months old, showed that it was 25 per cent, lower in the cretin than in the 2 infants. Talbot (Amer. Jour. Dis. of Child., vol. xii, p. 145, 1916). In mongoloid mixo-idiocy the me- tabolism is irregular as regards the relations between the various ele- ments of the urine (increased elimi- nation of amino-acids). Under thy- roid treatment, though, the metab- olism improved, showing better oxi- dation by diminished elimination of amino-acids and giving normal amount of residual nitrogen and of uric acid. G. Caronia (La Pediatria, 26, 336, 1918). Mongol or kalmtick idiots resemble cretins in many particulars. The mouth is kept open by the protruding and thickened tongue ; the hair is dry, scarce, and coarse ; the palatal arches are narrow, the development of the teeth is delayed, constipation is the rule, umbilical hernia is frequent, etc. But their skin is less rough, and the general development is less retarded, though that of the brain, judging from the degree of idiocy, must difi'er but little from that of a cretin's. In this class of idiots the palpebral fissures are narrow and slope upward from the nose; the epicanthus projects markedly over the inner canthus, as is the case in most Chinese. Nystagmus, i.e., os- cillatory movements of the eyeballs, is also common. Thyroid treatment though much less beneficial than in cretins, is, nevertheless, productive of good. The mental torpor is somewhat improved, the constipation and hernia are counteracted, and all functions seem to be activated. Achondroplasic dwarfs are in reality but cases of fetal rickets, are normal as to intelligence, but their face is that of the cretin, the skin, especially about the hands, also recalling that of the lat- ter. Other physical abnormalities are abnormal shortness and deformity of the limbs, marked narrowing of the palatal arch, and delay in the closure of the fontanelles. This condition, essen- tially due to morbid development of the bones and cartilages, is in no way influenced favorably by the use of thy- roid preparations. The dose should, of course, vary with the age of the patient from 34 grain (0.015 Gm.) by the mouth in a 1-year-old child to 3 grains (0.2 Gm.) in the adults. As tolerance varies, especially in children, small doses should be used at the start and very gradually increased until not more than lYz grains (0.1 Gm.) of desiccated thyroid in a child and 9 grains (0.6 Gm.) in an adult are given in divided doses daily. There is no condition in which the prevailing empirical method of administering remedies should be ANIMAL EXTRACTS (SAJOUS). 713 more rigidly guarded against than in this, since excessive doses of thyroid not only inhibit its beneficial effects by exciting violent catabolism, thus break- ing down the tissues instead of build- ing them up gradually, but they may, by doing so, cause death. [What unfavorable results have been re- corded can usually be ascribed to excessive doses. A certain critical author remarks, for instance, referring to personal experience of this sort: "There was no longitudinal growth of the bones nor any poisoning to be observed, but great bodily prostration and an augmentation of mental apathy, to- gether with emaciation dependent upon a loss of fat. From these unfavorable re- sults of therapy it is seen that the view is untenable that athyreosis is the cause of cretinism. These observations are the re- verse of the favorable ones made on the treatment of myxedema by thyroid gland, both in the young and in adults." The great bodily prostration, emaciation, in- crease of apathy, etc., speak for them- selves. They had been caused by the ex- cessive doses the critic had administered. C. E. DE M. S.] The doses in which thyroid extract is usually prescribed are many times too large. The ordinary dose is officially quoted as from 3 to 10 grains. There are very few people, except certain types of lunatics, who will tolerate such doses under any circumstances, and not even they are able to do so unless this dose is arrived at by a gradual increase from small beginnings. It is a clinical fact, well recognized by those who have any real experience in the use of the drug, that, the more the patient re- quires thyroid extract, the smaller should be the initial dose. Since the writer has been using it he has been driven back and back in his doses He now seldom begins with more than J4 grain three times a day. He never prescribes a larger dose than 5 grains thrice daily, and then only in pronounced myxedema after sev- eral weeks' treatment. He has had many patients who were unable to take more than y^o grain once a day, but this was in each case quite suffi- cient completely to protect them from the symptoms of which they origi- nally complained. In connection with the allotrophic disease, he suggests that the prophylactic dose for an adult should not exceed Ko grain three times daily, and that % grain three times daily is quite a sufficient therapeutic dose to start with. Leon- ard Williams (Practitioner, Nov., 1911). The writer summarizes his results in 41 cases of sporadic cretinism in respect to physical development, men- tal development, retardation of mental and physical development, and the age at which treatment was begun, and of- fers the following conclusions: (1) Under thyroid treatment, if begun early the physical development may reach normal. (2) When treatment is begun late the physical as well as the men- tal development may remain much be- low normal. (3) The improvement in the mental development is never as great as in the physical. (4) The earlier the treatment is begun the better the results as far as mental de- velopment is concerned. (5) In con- genital cases, if the treatment is be- gun after the first year, marked intel- lectual retardation persists. The later the treatment is begun the more marked will be the retardation. (6) To obtain good results the treatment must be regular and continuous. A case presented well illustrates this point. While the treatment was regu- lar the increase in height was 3^ inches in a year, whereas during the periods when it was irregular it was as low as M inch in a year. (7) In the acquired as against the congeni- tal form, the intellectual development is less retarded than the physical de- velopment. C. Herman (N. Y. State Jour, of Med. Aug., 1914). The danger signals are those of hy- perthyroidism, previously described, the principal of which are an increase of temperature beyond normal, tachy- cardia, digestive disturbances, dyspnea. 714 ANIMAL EXTRACTS (SAJOUS). and tremor. When any of these phe- nomena appear, the dose should be reduced until the temperature becomes normal — ^which may be one or two de- grees F. above the hypothermia usually observed in these cases. It should be remembered, however, that excessive doses may also cause hypothermia by inducing collapse. If the morbid ef- fects continue, the use of the remedy should be slopped a few days and then resumed with a smaller dose. Should the hyperthyroidism persist notwith- standing, Fowler's solution in small doses soon arrests it. A common un- toward effect is bending of the bones of the legs, owing to softening of the bones. The child should not be al- lowed to go about too much, or when bowing of the legs appears it should be placed in bed, as advised by Telford Smith. Case of tetany following an acci- dental overdose of thyroid extract in a girl aged 3 years who presented stigmata of cretinism. The treatment was suspended for a fortnight and the symptoms gradually disappeared. Then ^ grain of thy- roid extract was given t. i. d., in- creased to Vz grain. During the week after resuming the drug the "ac- coucheur hand" was again noticed. The dose was again reduced, but later increased. One month later a slight recurrence of the "accoucheur hand" compelled reduction of the dose of thyroid. Subsequently, though, on continuous treatment no recurrence of the tetany has been observed. G. W. R. Skene (Med. Review; Antisep- tic, May, 1911). [In the above case the toxic dose of thy- roid produced excessive catabolism and an accumulation of waste products in the blood. Hence, the tetany which is also produced when deficiency of thyroid also leads to accumulation of spasmogenic wastes because the latter are not submitted rapidly enough to hydrolysis, a process for which the thyroid secretion prepares the wastes by sensitizing them. C. E. DE M. S.] An important feature of the thyroid treatment of cretinism is the necessity in practically all cases of continuing it to prevent recurrence. The only per- manent benefit when thyroid is discon- tinued is the skeletal growth, though the original morbid phenomena never return with the same intensity. In an idiotic child, Payr, director of the Leipsic Surgical Clinic, implanted a part of a normal thyroid gland in the kidney. Mental regeneration is said to have immediately started and within 1 month the child was dis- missed from the hospital with the im- planted thyroid gland maintaining its functional capacity in the new body. Payr (Post-Graduate, June, 1912). In several cretins in whom cessa- tion of thyroid feeding led rapidly to a recurrence of myxedema the writers were led to try practical autotrans- plantation of the thyroid into the thy- roid capsule with success in all cases. There should be a minimum disturb- ance of the blood supply in the region in which the transplant is placed, and foreign bodies, such as suture ma- terial, should not come into contact with the transplant. The varying de- gree to which a homotransplant takes depends on the amount of reaction between the host and the tissue trans- planted. A familial relationship and probably the early age of the animals on which operation was performed were shown to be important features of success. Hess and Strauss (Arch, of Internal Med., Apr., 1917). Several cretins occasionally occur in the same family, from the same mother, long intervals between births indicating the permanence of the patho- genic influence in the parent. Herman H. Sanderson (Jour, of the Mich. State Med. Soc, April. 1906), for example, observed 3 cases in one family, the patients being 21, 11, and 8 years of ANIMAL EXTFL\CTS (SAJOUS). 715 age, respectively. This points to the need of administering thyroid to the mother after the birth of a cretin, and during any subsequent pregnancy. Occasionally a case is met in which instability of the gland may manifest by deficient activity at one time and abnormal activity at another. Case of a diminutive woman aged 33, who exhibited alternately, and at times even in conjunction, pro- nounced symptoms of hypothyroidia and hyperthyroidia. At night the pa- tient passed into a condition verging on myxedema, while in the post men- strual period her condition suggested Graves's disease. Intervening be- tween the hypothyroidia and hyper- thyroidia were normal periods, the latter amounting, however, only to a few days in each month. It is as- cribed to variations in the circulation through the thyroid, inducing alter- nate states of inertia and overactiv- ity in its function. Leopold-Levi (Presse med., June 10, 1918). Myxedema. — Thyroid preparations are no less efficacious in this disease, which typifies hypothyroidism, in the adult than in cretinism, of which, in fact, this disorder is the prototype in adults. Here, again, we obtain those striking changes which clearly indicate that the remedy replaces in the organ- ism a constituent necessary to the vital process itself, and the least deficiency of which impairs all functions. This is further shown by the necessity of ad- ministering it continuously, year in and year out, as in cretinism, to prevent re- currence. Under the influence of thyroid prep- arations the morbid symptoms disap- pear. The dense, swollen tissues rap- idly recede, causing loss of weight ; the projecting abdomen resumes its nor- mal contour; the skin loses its rough- ness and dryness; the hair grows more or less abundantly ; the face loses its coarse and expressionless appearance, the wax-yellow color of the skin being replaced by a normal hue ; the cyanosis of the lips, ears, and nose disappears. Even the slow and monotonous speech and mental torpor are promptly done away with, and if the case happens in an adolescent stunted by the disease growth is resumed and progresses rap- idly, as in cretinism. The physiolog- ical action is precisely that defined un- der the preceding heading, since we again meet with a rise of temperature and all the phenomena that denote in- creased metabolic activity, including a marked increase in the urea excretion. ^Menstruation, frequently suspended, soon returns. The appetite markedly increases, and the patient experiences a feeling of well-being The writer reviewed the history of the first case of myxedema success- fully treated by thyroid extract. The results obtained not only afforded definite proof that the thyroid gland produced an internal secretion, but showed that the thyroid insufficiency of m3'xedema in man could be made good b^r maintaining an adequate supply of thyroidal hormones from an external source. This patient, a woman of 46 when the treatment was begun, in 1891, lived until early in 1919, when she died at the age of 74. By the regular and continued use of thyroid extract she was enabled to live in good health for over 28 years after she had reached an advanced stage of myxedema. During this period she consumed over 9 quarts of liquid thyroid extract or its equiv- alent, prepared from the thyroid glands of more than 870 sheep. George R. Murray (Brit. Med. Jour., Mar. 13, 1920). Myxedema is insidious in its course; this renders an early diag- nosis difficult. The importance of recognizing this disease lies in the fact that a sovereign remedy for it exists and that, unrecognized and 716 ANIMAL EXTRACTS (SAJOUS). long overlooked, such cases suffer serious physical and mental develop- ments. J. M. Anders (Trans. Amer. Climatol. Assoc; N. Y. Med. Jour., Dec. 7, 1921). The dose generally employed in this disease is, as a rule, too large ; 1 grain (0.065 Gm.) of desiccated extract daily, gradually increased until 2 grains (0.12 Gm.) are given t.i.d. Even smaller doses have given favorable results. Inasmuch as myxedematous patients are, as a rule, more susceptible to thy- roid preparations than normal subjects, it is always best to begin with small doses, since the degree of activity of the patient's own thyroid, though greatly reduced, is an unknown quan- tity. The presence of unexpected ac- tivity is the main underlying cause of the so-called "susceptibility" often met with, a very small dose of the desic- cated thyroid sufficing in such patients to raise the standard of thyroid activity to its normal level. Again, as I have shown elsewhere (see "Internal Secre- tions," 1st ed., p. 1139, 1907). there is a true cumulative action of the thyroid secretion (thyroiodase) when thyroid preparations are administered, and there comes a time when toxic phe- nomena appear, even under the influ- ence of very small doses. The tem- perature is the best guide. As it is be- low normal in all cases, the doses should be regulated in such a manner as to raise it to normal, reducing them as 98.6° F. (37^ C.) is exceeded. The quantity required — usually somewhat larger in winter than in summer— by each patient may thus be readily de- termined while avoiding cumulative efifects. In some cases it is well to ascertain whether a low blood-pressure is not perpetuating the peripheral hypother- mia by causing the blood to recede to the deeper great trunks. This may be (lone by giving strychnine simulta- neously in doses of %o grain (0.0016 Gm.) three times daily. By stimulating the vasomotor center, it causes the ves- sels to contract, and thus to project the circulating arterial blood into the pe- ripheral capillaries. Strychnine, more- over, as shown by I. N. Love, tends to prevent the untoward efifects of thyroid l^reparations. An important feature of the thyroid treatment of myxedema is that the pa- tients should be kept in bed the first few weeks and not allowed to get up suddenly, to avoid sudden syncope — the cause of death in several cases on rec- ord. This precaution is especially nec- essary in aged and weak patients and quite as much where the improvement is rapid as in less favorable cases. As emphasized by Combe, Seymour Tay- lor, and others, alcohol should not be used during the treatment. Bourneville, Lancereaux, and other clinicians have called attention to the fact that symptoms of myxedema do not appear in infants until they are weaned. This is because the mother supplies her suckling what thyroid se- cretion it needs to satisfy the needs of its cellular metabolism. Thyroid ad- ministered to a nursing mother is also transferred to the nursling in such a degree, in fact, that the latter may pre- sent toxic phenomena. This suggests additional caution when the remedy is used in myxedematous women during pregnancy and lactation. Thyroid feeding was found by the writers to increase the catalase of the blood while decreasing it in the heart and probably in the fat and skeletal muscles. The increased blood-cata- lase may account for the increased oxidation in animals given thyroid. Burge. Kennedy, and Neill (Amer. Jour, of Physiol.. June, 1917). ANIMAL EXTRACTS (SAJOUS). 717 Contraindications. — When any ady- namic cardiac disorder is present, the initial dose should be very small and very gradually increased, giving digi- talis simultaneously if indicated by the cardiac trouble. When angina pec- toris accompanies myxedema, small doses of thyroid are beneficial, espe- cially if the patient is placed on a vege- table diet. beneficial efifects of the thyroid prep- aration. The danger sigtials when thyroid is used in myxedema are, as in cretin- ism : tachycardia, palpitations, prostra- tion with sweating, rapid emaciation, gastrointestinal disorders, anemia, head- ache, and in some cases excitement recalling hysteria. When the doses (even though small) are too large for smt'_ * Fig. 1.— True myxedema. (Hertoglie: Bul- letin de I'Academie Royale de Medecine de Belgique.) Occasionally aged subjects fail to respond to the thyroid treatment alone, and the disease progresses until mental aberration, melancholia, or even mani- acal disorders supervene. The de- pressed forms of mental disorder are probably due to the low blood-pressure which characterizes the disease, and which the thyroid tends to increase. Strychnine counteracts this untoward action, however, while enhancing the Fig. 2.— The same patient after thyroid treatment. (Hertor/lie: Bulletin de I'Acade- mie Royale de Medecine de Belgique.) the patient, urticaria may appear. This is due to cutaneous irritation caused by the more or less toxic wastes produced in excess owing to the excessive catab- olism induced, and which the kidneys cannot eliminate with sufficient rapid- ity. Cessation of the drug for a few days usually causes all these morbid efifects to disappear, after which the remedy may be resumed in very small doses. 718 ANIMAL EXTRACTS (SAJOUS). After recovery, the patient's health can usually be maintained, i.e., recur- rence of the disease prevented, by ad- ministering small doses, 1 grain (0.065 Gm.) daily or every other day — just enough to sustain the temperature up to normal. In winter it is sometimes nec- essary to increase the dose somewhat to obtain this result. The prolonged Fig. 3.— True myxedema; sister of patient in Figs. 1 and 2. (Ilrrtoghe: Bulletin de TAcademie Royalc de Medecine de Belgique.) use of the remedy does not, with rare exceptions, diminish the need of it to ward off the disease ; cessation after several year's use will be followed by prompt recurrence of the morbid phe- nomena. Case in a man of 36 years in which, after recover}- from the initial treat- ment by the thyroid extract (which lasted two months in continuous dos- age"), the patient was never under treatment longer than foi:r weeks at one time. The longest respite from thyroid therapy was for a period ex- tending from May, 1907, to October of the same year, a period of five months; at the end of this time some of the old symptoms were again in evidence, namely, characteristic color, loss of expression, swelling and puffi- ness under the eyes; the mentality, however, continued good. The pa- tient himself wanted to be placed under treatment again. An interest- ing feature of the case, aside from its rarity in these parts, is that if the pa- tient takes more than three tablets a day, now that a cure is established, or continues the treatment for more than three weeks, he soon shows the symptoms of exophthalmic goiter, namely, nervousness, sleeplessness, slight exophthalmos, nausea, some- times vomiting and general weakness. S. E. Simmons (Jour. Amer. Med. Assoc, May 15, 1909). Occasionally a case is met with in which the thyroid treatment is followed by permanent recovery. Such cases are probably instances of temporary myxe- dema due to obstruction of the lym- phatics through which the secretion gains access to the general circulation, or to some other factor interfering temporarily with the functions of the gland. Between the cases in which contin- uous after-treatment is required and those that proceed to recovery are some in which respites of several weeks in the after-treatment are required to obtain the best results. This is a re- sult obtained, however, only when large doses of thyroid are used in the after- treatment. There is danger in such cases of causing hyperthyroidism, i.e., the .symptoms of exophthalmic goiter, and it is preferable to reduce the dose until the exact quantity required con- tinuously to keep the patient well is ascertained. Thyroid grafting has been performed successfully in animals, especially by ANIMAL EXTRACTS (SAJULS). 719 Christian!, and more recently in human subjects suffering- from myxedema or cretinism. In the earlier operations, the improvement lasted only as long as the secretion that happened to be in the implanted tissues lasted, but in re- cent years better results have been ob- tained, the grafted fragments of thy- roid assuming physiological functions to a sufficient degree to prevent recur- rence of the disease. Case of a young woman who, be- coming tired of the preventive treat- ment by thyroid, requested a substi- tute. The writers inserted portions of a sheep's thyroid gland in a series of grafts under her skin on two occa- sions three and a half months apart. The thyroid feeding was gradually diminished until it was reduced to a few drops a day of a liquid extract. About six months after the second transplantation the patient was de- livered at term of a well-developed healthy infant. It was observed that during the latter months of her preg- nancy the grafts became enlarged, evidently from congestion, being af- fected like the normal thyroid by the pregnancy. The successful termina- tion of the pregnancy was ascribed in great part to the thyroid treatment, and especially the implantation of the functionally active thyroid under the skin. Lannelongue, in a case of a myxedematous infant, had previously implanted the first fragment of a sheep's thyroid in the human subject. The child's condition appeared im- proved, and the development of the disease became a little less active. Charrin and Christian! (Le Bull, medicale, July 11. 1906^. The best results can certainly be ob- tained with repeated implantation of small scraps, and for this it is better to implant the scraps in the subcutaneous tissue (Christian]) or in the peritoneal tissue (von Eiselsberg). Series of personal experiments in thyroid implantation showed that thy- roid tissue of the guinea-pig trans- planted in the same animal heals most easily and best .'hen the transplanta- tion is made into the subcutaneous connective tissue; likewise, the peri- toneal cavity shows itself a very favorable implantation site; that transplantations into the spleen heal fairly well, but the end results are less good and not so certain as those ob- tained when one uses as implantation sites the two places above named; the liver and the bone-marrow are very unfavorable organs for the healing in the thyroid tissue; that thyroid trans- plantation promises in general more fruitful results if one avoids all bleed- ing in the pocket destined to receive the graft; that if one transplants the thyroid tissue in conjunction with the connective-tissue capsule pertain- ing to it, it is to be observed that the follicles in the vicinity of this capsule are better preserved and more numer- ous than the more remote follicles; that the best results are attained if one transplants into the subcutaneous tissue very thin slices of thyroid tis- sue instead of larger pieces; one con- dition is that one of the surfaces of the implanted piece is covered by the connective-tissue capsule of the thy- roid. Carraro (Deut. Zeit. f. Chir., Feb., 1909). The more recent work of Payr ( 1912) and of Hess and Strauss (1917j has been reviewed under the preceding heading. Obesity. — The treatment of this condition by means of thyroid prep- arations was far more in vogue a few years ago than at present, owing mainly to its indiscriminate use by laymen, and to the use of excessive doses by the profession. Both these features were the cause of dangerous phenomena (and sometimes death) during the course of treatment, or of pernicious after-afTects. \\'hen thyroid prepara- tions are used intelligently, however, adjusting the dose to the needs of each 720 ANIMAL EXTRACTS (SAJOUS). case, and regulating judiciously the concomitant diet — which in some cases means an increase — a great deal of good may be done in the great major- ity of cases, besides improving the ap- l)earance of the patient and his general well-being. (See article on Obesity, in the seventh volume.) The cases in which thyroid prepara- tions act favorably are those in which metabolic activity, especially its cata- bolic phase, is deficient. The fat, ruddy boy or the plethoric, vigorous, red- faced high-liver do not belong to this category. Those that do are pale, flabby, anemic, in most instances fe- males between 25 and 45 in which the heart beat is weak, sometimes irregular and rapid with compressible pulse. The fat in such is more or less irreg- ularly distributed in the subcutaneous tissues; they sufifer from dyspnea, es- pecially on exertion, and fall asleep readily at any time. Such cases are in reality instances of mild myxedema in which the thyroid does not supply quite enough secretion to satisfy the needs of the organism. It is not a question of overeating with them ; such patients, in fact, are, as a rule, abstemious, the slowness of their tissue exchanges causing them to have but little appetite. Unable to burn up their carbohydrates, sugars, starches, and fats as fast as they are ingested, fat steadily accumu- lates in all tissues. Thyroid preparations, when judi- ciously used under such circumstances, are of value mainly because the role of thyroid secretion they replace is pre- cisely— from my viewpoint — to en- hance the catabolic phase of metab- olism, essentially the function at fault in obesity. The fat-cell is rendered more susceptible to oxidation— along with the other tissues — and the excess of fat is steadily consumed. Series of about 100 cases of obesity in which thyroid extract was used. No untoward symptoms were noticed in any of the cases, malaise, head- ache, palpitation, and nervous de- rangement being entirely absent. Al- buminuria was not seen at any time. The thyroid gland used in all in- stances was B. W. & Co. tabloids. The initial dose was lYz grains with each meal, either mixed with the food or taken with a little water. After seven days the dose was in- creased to 5 grains with each meal, and this dose was not increased in any case. The tabloids were crushed before being taken. In the successful cases summarized below no alteration in diet was ordered, the patient eating and drinking anything he or she de- sired. Alcohol was, however, strictl)' prohibited in any form. Of 78 females treated 69 were be- tween 25 and 45; their average weekly loss was 2J/2 to 4 pounds, and the re- sult was permanent cure; 9 were be- tween 15 and 19, and there was no permanent result in any of them. Of 25 men 9 were between 30 and 47; they lost on an average 2 to ZYi pounds weekly; the cure was perma- nent; 11 men between 30 and 47 lost 1 to \y2 pounds on an average, but the result was not permanent; on 5, between 14 and 17, there was no effect at all. W. J. Hoyten (Brit. Med. Jour., July 28, 1906). The writer emphasizes the neces- sity for distinguishing between obe- sity due to overeating or laziness and obesity for which some constitu- tional cause is responsible, as treat- ment varies widely with the factors involved. In the exogenous type, overeating and lack of exercise may combine to induce the obesity; the tendency to overeat and to refrain from exercise may be due to abnor- mal instincts, possibly the result of reflexes perverted from normal by some chemical influence. It is usu- ally possible in time to train these ANIMAL EXTRACTS (SAJOUS). 721 instincts into normal routes. Reason- ing, compulsion and psychic measures are usualh- necessary, in addition to diet and exercise, in these cases. The other type of obesity, the endog- enous, constitutional type, he regards as traceable to abnormal thyroid func- tioning. Congenital or acquired weakness or degeneration of the thy- roid maj^ induce the obesity directly or the thyroid may become a factor in the obesity only secondarily, as in case of pancreas disease (demon- strated only experimentally as yet) ; disease in the ovaries or testicles (deficiency of the interstitial sub- stance); disease in the pituitary body (adiposo-genital dystrophy); disease in the pineal gland or thymus (both dubious). There may also be a com- bination of both the exogenous and endogenous type, especially in the young. Throughout the endogenous forms, abnormal thyroid functioning is com- mon to all, and treatment of consti- tutional obesity must be based on thyroid treatment. It is unquestion- able now that the reliance on thyroid treatment is increasing, the dread of it diminishing. The dangers from thyroid treat- ment are just as great as ever, but we know better how to watch out for them and guard against them. The writer adds that even in cases amenable to systematic dietetic meas- ures alone, the prolonged restriction of the diet seems to him more of an evil than a course of thyroid treatment. With this the diet need not be so strictl}' regulated and the effect of the thyroid treatment is often per- manent, so that the patients can eat like other people afterward without bringing back the obesity. During the thyroid course ample provision of albumin should be en- sured. The urine should be ex- amined often for sugar. The tendency to acceleration of the heart action and reduction in blood-pressure can be warded off b}- daily small doses of some digitalis preparation. Thyroid treatment is not required in the exogenous type of obesity, diet and exercise answer the purpose, and without training in this line the obe- sity will return whether thyroid treatment has been taken or not. Ap- paratus to reduce obesity by electric contractions in the muscles are ridi- culed bj" the writer as unable to in- duce anj' appreciable effect on the oxidation processes beyond the effect of suggestion. In conclusion he urges physicians to keep up a con- stant warfare against the "patent medicines'' advertised to cure various ills, and especially the obesity cures, as they are by no means harmless remedies. Von Xoorden (Jour. Amer. Med. Assoc; Therap. Monats., Jan., 1915). The writers observed the case of a woman who had been thin until the age of 18, when she contracted syph- ilis; she then began to increase in weight, finally reaching 157 kg. (345 lbs.), although only 1.6 meters (5 ft. 3 in.) tall. The pituitary was found normal, but both thyroid and ovaries were pathologic. There were 7,756,200 erythrocytes to 11,320 leucocytes, with Arneth dis- placement to the left. There was verj' little fat around the heart, but the myocardium showed degeneration, and this was probably responsible for the sudden death. The histologic findings in the thy- mus showed functional persistence. Maraiion and Bonilla (Revue Neurol., Sept., 1920). Contraindications to the use of thy- roid preparations in obesity have been elaborated by various obsei^-ers; but perusal of their work indicates clearly that they have been administering ex- cessive doses. Such doses are always dangerous in the obese, since the heart is itself invariably fatt^^ wdiile, con- versely, small doses are always help- ful because they very gradually rid 1^6 722 AXIMAL EXTRACTS (SAJOUS). the heart of the fat which compro- mises its functions and eventually causes death when the patient has not been carried off by some intercurrent disorder. Even moderate doses have not proven harmful when the patient was under medical surveillance. The dose of desiccated thyroid need not exceed 1 grain (0.65 Gm.) three times daily in any case. This suffices to cause a decrease of weight of from one to three pounds a week, and some- times more, Anders ("Practice," 8th ed., p. 1276) having observed in 2 cases under this dose "a progressive loss of weight at the rate of 4 to 6 pounds per week, respectively, with- out injury to the general health." Such doses do not impose upon the patient the need of modifying his usual mode of living, and his diet need not. unless excessive, be altered. When the obesity is accompanied by weakness, the appetite is usually in- creased, especially when, as is my custom, gr. 1/50 (0.0012 Gm.) of strychnine is given with each dose of desiccated thyroid. The patient does best under these conditions when lean meats, plainly broiled, roasted, or stewed, constitute the in- crease of his dietary. This treatment is valuable in another direction : it tends to counteract any tendency to constipation that may be present. Danger signals or untozi'ard effects are not met with when small doses are given, as previously stated, but the physician has occasionally to treat some victim of excessive dosage. A case was observed by Notthaft in which a man took for obesity nearly 1000 5-grain tablets of thyroid extract within five weeks. After the first three weeks he began rapidly to develop the symptoms of acute Graves's disease. When thyroid was stopped and the patient was put upon arsenic all the symptoms disappeared quickly, excepting the eye changes and the goiter, which were still nota- ble for about six months. The untoward effects most fre- quently met with in obese subjects are of cardiac origin : marked discomfort in the precordia, dyspnea with tend- ency to heart-failure. In some in- stances this has been followed by death when marked fatty degeneration hap- pened to be present. But, as stated, these do not occur when small doses — 1 grain (0.065 Gm.) of the desiccated thyroid — are used. Even the greatest watchfulness will not prevent toxic ef- fects when large doses are adminis- tered, since the accumulation of the thyroid principle proceeds at a rapid rate and the milder symptoms of thy- roidism are almost at once followed by its acute manifestations — those pre- viouslv described. Miscellaneous Disorders. — In the foregoing diseases thyroid treatment may be regarded as a specific, none other affording satisfactory results. Its use is being extolled in many other dis- orders; but it is still a question whether it procures better effects or even as good results as other available rem- edies. These will be considered in their alphabetical order. Acromegaly. — The reports of cases of this disease treated with thyroid have been insufficient to warrant a con- clusion, the results having been contra- dictory. This is probably due to their empirical use. According to my inter- pretation of the disease : hypertrophy of the pituitary causes excessive activ- ity of the adrenals and thyroid (which the pitultar}' governs) for a time, i.e., during the sthenic period of the disease. ANIMAL EXTRACTS (SAJOUS). 72Z Given during this period, thyroid prep- arations can only, therefore, add fuel to the fire and do harm. There comes a time, however, usually after several years, when the enlargement of the pit- uitary ceases and degeneration of this organ occurs, initiating the asthenic period. The adrenals and thyroid then usually reduce their functional ac- tivity inordinately, and oxidation and metabolism are inadequate for the per- petuation of the vital functions. Here thyroid (preferably with adrenal) is useful and may serve greatly to pro- long life. Instances of benefit in advanced cases have been published by various authors. Thus, Sears observed a case treated with dried thyroid gland in gradually increasing doses until 12 grains a day were taken, besides galvanism and tonics. Three months later she w^as feeling very much better, her memory had improved, and she spoke and moved more rapidly. She had lost over 20 pounds in weight, but felt stronger. The history of the case and the marked physical changes leave little doubt that it was a case of acromegaly, but certain anomalous symptoms — such as the pufify conditions of the eyelids, which may, however, have been simply the result of anemia, though its appear- ance was somewhat different ; the slow speech, and the altered mental state — suggested that her condition was also associated with a loss of function of the thyroid gland. Rolleston also refers to a woman 26 years old who had suffered from acro- megaly for upward of two years, and who for a period of five months had been treated with mixed pituitary and thyroid extracts, with great improve- ment. At the present writing (1921), however, the wdiole subject is being considered from another viewpoint which is reviewed at length in the article on Acromegaly in the present volume. Arteriosclerosis. — As is well known, the iodides are used with benefit in this condition. It naturally follows that thyroid preparations, which owe their therapeutic activity to the iodine in organic combination they contain, should likewise prove beneficial. This Case illustrating: the association of acromegaly and g-oiter. (G. K. Murray.) proved true in cases reported by Lan- cereaux (La Semaine med., Jan. 4, 1899). James Barr (Brit. Med. Jour., Jan. 20, 1906), and other authorities. The favorable action of thyroid in these cases, however, necessitates the use of large doses — 5 grains (0.3 Gm.) three times a day— enough to cause general vasodilation. As such doses are unsafe in aged subjects, who constitute the greatest proportion of our cases, its use should be limited to middle-aged patients, therefore, reserving the io- dides for the former. Sir James Barr, in fact, prefers iodine to thyroid. Arthritis, Chronic Rheumatoid. — In this disease good results are occa- 724 ANIMAL EXTRACTS (SAJOUS). sionally obtained when no other agent will produce the least effect. Leopold- Levi and de Rothschild, for example, describe the phenoniiena observed in 2 cases of chronic rheumatism with hydrarthrosis in which thyroid extract proved of distinct value. In 1 of these the hydrarthrosis followed a fall from a bicycle, and was the precursor of attacks of muscular rheumatism, all the joints being gradually involved in the morbid process. Notwithstanding seasons at Aix-les-Bains, Dax, and other stations, the patient became quite impotent, having even to be fed. The usual remedies proved unavailing, though aspirin and iodine seemed, at least for a while, to be of some benefit. The patient's condition becoming stead- ily worse, thyroid extract was tried, be- ginning with P/2 grains every other day during ten days, followed, after five days, by resumption of the rem- edy; then giving again only l|o grains every other day. This dose was grad- ually increased until, eleven months later, the patient was taking 7^2 grains, in divided doses, daily. Good results have also been recorded by Revilliod, Lancereaux, and others. The beneficial effects of the drug be- come self-evident when its action and the pathogenesis of chronic rheumatism are interpreted from my standpoint. Briefly, while I have ascribed this dis- ease to "inadequate catabolism of tissue wastes, and excitation, by the toxic products formed, of the vasomotor center" thyroid extract, as stated in the foregoing pages, enhances general oxi- dation and the destruction of wastes, by increasing the blood's asset in op- sonin and autoantitoxin. Thus, increase of appetite was the first effect noted in the cases referred to above ; this is a normal result, since the greater cellular activity and catab- olism created a greater demand for foodstuffs. Increased heat production soon replaced the marked and constant chilliness from which the patient suf- fered— an effect due to the marked in- crease of oxidation the thyroid extract engendered throughout the body. The dose was increased to 1^ grains one day, then to 3 grains the next, this being continued ten days. After a period of rest of five days, 3 grains were again given daily. The pain became less — a fact due to decrease of the vascular ten- sion, owing to increased destruction of the toxic wastes which, as I have l)ointed out elsewhere, excite the vaso- motor center, thus causing constriction of all arteries. The sensory nerve-ter- minals being relieved of the hyperemia which caused the pain, the latter be- came less marked in proportion. Closely connected with this beneficial action was the effect on the joints, viz.: the hydrarthrosis became reduced. Be- ing also due to excessive vascular ten- sion, it is plain that by causing vaso- dilation, in the manner just explained, thyroid extract caused the excess of fluid to leave the joints. The dose be- ing still further increased until 7^2 grains were taken daily, eniaciation occurred — a well-known effect due to excessive catabolism provoked by large doses of thyroid extract. Eleven months' treatment brought Leopold-Levi and de Rothschild's case back to a condition of comfort, the joints having resumed their shape and flexibility — with the exception of one knee, which remained ankylosed — ow- ing doubtless to fibrosis, a condition beyond the reach of the remedy. This does not militate against its use, how- ever; it simply shows that the treat- ment was resorted to too late to avoid ANIMAL EXTRACTS (SAJOUS). 725 irremediable organic lesions. The au- thors, in fact, refer to a case treated by Parhon and Papinian (Presse med., No. 1, p. 3, 1905) in which thyroid extract had produced, though the dis- ease was of twenty-four years' stand- ing, "a true regeneration.'' When lYz grains f in five divided doses) daily had been given some time, palpitations, tachycardia, and arrhythmia appeared. On withdrawing the remedy these un- toward effects ceased, but recurred as soon as its use was resumed. This affords additional evidence in support of a fact I have often emphasized, viz. : that the beneficial eft'ects of thyroid extract are obtained only when small doses are used. Case of rheumatoid arthritis in which the writer was struck by the patient's rough, dry, harsh skin, crisp hair, husky voice, and deep supra- sternal notch; the prominence of the trachea, and apparent absence of thy- roid gland, analogy to other condi- tions suggesting deficiency of thyroid secretion. Accordingly, the extract of thyroid was administered in doses of 5 grains three times daily, together with adju- vant treatment to be mentioned pres- ently. In a month the results were remarkable. The patient could struggle on crutches from one room to another, his appetite returned, and pain was almost gone. In three months he could walk with two sticks, and in eighteen months he was able to walk three miles with the aid of one stick. His elbows and should- ers have regained their mobility al- most entirely, and he has been for a year able to do without his thyroid extract without a relapse. At the present date he is able to get about well, with slight flexion of one knee and some metacarpophalangeal de- formity, but is fat and well. Two additional cases in which marked improvement occurred. In the writer's opinion the group of cases likely to receive benefit are those in which changes are chiefly confined to the synovial membranes, without erosion of cartilage or ebur- nation of bone, such cases in fact as Schiiller describes as "chronic villous arthritis." Wilson (Brit. Med. Jour., Dec. 10, 1910). After prolonged observation the author is inclined to believe that very few cases of long-standing arthritis exist without some degree of thyroid failure. There can be little doubt that rheumatoid arthritis (including both osteoarthritis and chronic infec- tious arthritis) is the result of chronic toxemia following an original acute condition in the majority of instances. In the early stages some or all of the following symptoms may occur: Changes in skin pigmenta- tion; patches varj-ing from a lemon color to brown; spots like bruises oc- curring spontaneously; occasionally white spots; vasomotor disturbances; perspiring hands and feet, or paroxys- mal perspirations of other restricted areas; rashes; local anemias or as- phyxia; shooting pains; muscular cramps; paresthesias; neuralgic head- aches; gradually increasing flatfoot; muscular weakness; morning stiff- ness, etc. These symptoms may pre- cede any noticeable arthritis. The poisons that are affecting the system as a whole may damage the thyroid, and, although at first there may be excessive secretion of this gland, sooner or later more or less failure occurs, and then is the time to be- gin giving thyroid extract. Care should be taken to distinguish between thj'roid failure and failure of the pituitary body. The former is associated with a slow pulse, the lat- ter with a frequent pulse. In either case the patient may be puffy and lethargic. In simple obesity, on the other hand, patients are often bright mentally and active physically. As to the diet in rheumatoid arth- ritis, meat, speaking generally, should be eaten; but if the thyroid function is imperfect, meat becomes danger- ous unless sparingly taken. 726 ANIMAL EXTRACTS (SAJOUS). It is best to give a small dose of thyroid at first. For some patients the author prescribes as little as 1^ grains (0.1 Gm.) once daily. They lack resisting power and cannot with- stand the toxic effects of excessive doses. As a precaution it is well to allow a few days' interval from time to time in any case. The pulse should be watched, and if blood- pressure records are not obtainable any undue fall should be noted by the trained finger. Thyroid treatment in chronic ar- thritis is, of course, merely an ad- junct, and cannot be depended upon alone to deal successfully with the disease. Septic foci should be looked for and dealt with, and the author be- lieves that in these cases all teeth should be removed, since few are healthy. Teeth may be responsible for much gastrointestinal catarrh even when there is no actual pyorrhea. In cases where thyroid failure has become thoroughly established, it is necessary for the patient to take thy- roid in suitable doses for the rest of his life; W. J. Midelton (Pract., Jan., 1912). The writer observed the case of a girl of 15 who had suffered 3 severe attacks of acute articular rheumatism, the last of which left a contracture of the tendons of both hands, render- ing them useless. Various anti-rheu- matic remedies and physical measures having proved ineffective 10 days, thyroid therapy, with no associate treatment whatever was sulistituted. After 6 days of treatment the bene- fit was apparent and at the end of 3 weeks the normal conditions of the hands had been fully restored. R. G. Pizarro (Sem. medica, xxiii, 445, 1916). The writer has cured a number of cases with thyroid alone, where signs of hypothyroidism and dcrmographia were present. Leopold-Levi has em- phasized the importance of ascertain- ing the presence of hypothyroid stig- mata. Blind (Paris Med., June 18, 1921). When the salicylates fail in rheu- matism, the concomitant administra- tion of thyroid in small doses will cause the former to act. Cancer. — Thyroid preparations have been tried by a number of clinicians in this disease. Some have obtained favorable results ; others observed only temporary benefit; others again have observed no effect whatever. There are many indications, however, that, in due time, will prove thyroid to be a valuable aj^ent in this condition. Report of several cases treated by the writer with no other agent than thyroid in which recovery has per- sisted over 9 years, the cases treated including such forms as mammary and uterine cancer. Robert Bell (Trans. Brit. Gynec. Soc, vol. v, 1896). In mammary cancer the use of thy- roid alone was sufficient to cause the entire disappearance of the growth. In this case the writers began the treatment by giving a daily dose of 3 grains (0.2 Gm.) and increasing the dosage until the patient was taking 15 grains (1 Gm.) a day. At the time of this reporting, 2 years there- after the patient was in perfect health and no trace of the cancerous growth could be found. Page and Bishop (Lancet, May 28, 1898). Thyroid gave better results in the treatment of cancer than any other agent. Dennis (Jour. Amer. Med. Assoc, Oct. 19, 1901). In a very severe case of cancer — the diagnosis and prognosis being confirmed by Sir Francis Laking — in which the termination was fast ap- proaching and the pain and suffering were intense, the writer obtained re- sults bordering on the supernatural. Convalescence began immediately, so that by the end of January — thyroid extract, 5 grains (0.3 Gm.) quickly increased to 20 grains (1.3 Gm.) daily, having been begun at the end of November — the patient was up and free from pain. In the following ANIMAL EXTRACTS (SAJOUS). 727 October — nearly a year afterward — she "was quite well and was follow- ing an active life." H. A. Beaver (Brit. Med. Jour.. Feb. 1, 1902). The writer tried experimentally during the past 25 years many drugs and many gland extracts, including all vaunted agents from mixed tox- ins to the last recommended gland extract, and with the exception of thyroid extract, and possibly arsenic, he has never seen any definite benefit from their use. A. R. Robinson (N. Y. Med. Jour., Dec. 29, 1906). Report of a case of multiple car- cinoma of the skin and subcutaneous tissue, in a widow aged 61. The original growth had been removed a year previously, but others since ap- peared, and the patient's health was suffering severely. Thyroid was tried, starting with 5 grains, gradually in- creased to 15 grains daily. The pa- tient quicklj- showed improvement; palpitation, sickness, and emaciation gradually disappeared along with the growths themselves. In less than three months they had entirely gone. The patient was practically well and had recovered her lost weight of 3 stone. This occurred in 1901. Ten years later, the patient was still well. E. Hughes Jones (Brit. Med. Jour., Feb. 25, 1911). The causes which led many clini- cians to shun thyroid were, first, too large dosage, and, second, unreliabil- ity as regards physiological action of the then prevailing preparations. Internists are found prescribing a daily dose of 3 to 6 grains (0.2 to 0.4 Gm.), with beneficial and not un- toward results. Buford starts with V^. to 3 grains (0.03 to 0.2 Gm.) of the desiccated thyroid every 12 hours, and gradually increases the dose, while Stern, Percy, Middleton, Leopold-Levi, Firth, Dupug, Valmorin, Variot, Minoret, Siegmund and many other observers, all are ardent advocates of the minimuin dose. While there is no doubt that the untoward effects noted by the pioneer clinicians were to a large extent due to the excessive doses employed, yet the second factor, i.e., the unrelia- bility of the preparations, was the greatest contributing element. H. H. Redfield (Med. Summary, Aug., 1915). Cancer is a blood disease which has resulted from persistent auto- toxemia. Health}^ cell metabolism is gradually replaced by cell metamor- phosis, which results in these meta- morphosed cells departing from physiological control, and assuining the character of fungi. These grow upon and not zcithin the tissue, as be- nign tumors do. Moreover, these are able to exist and thrive only upon a vitiated soil, which in this instance is the blood. Fungi likewise are able to exist only upon a polluted soil. So long as the thyroid gland is in a health^' condition healthy cell metabolism will continue; but this can only be the outcome of this gland and every other gland being supplied by non-toxic blood. Other- wise its functional activity will be re- duced, and so we invariably find that hypothyroidism is in existence. More- over, there also coexists atrophy of this gland in cancer subjects. Robert Bell (Med. Rec, Feb. 28, 1920). For the time being, thyroid prepara- tions should be used only in absolutely inoperable cases, surgery having given far better results than any other method, including X-rays and thyroid preparations. In the second place, it is a mistake to attribute specific or even curative properties to thyroid preparations alone. They only assist in the curative process by facilitating pro- teolysis, i.e., breaking down of the growth. The detritus is such that after its use the kidneys are greatly exposed, and cases have been reported in which fatal nephritis followed the use of large doses. Such doses are, therefore, dangerous. Small doses do quite as well ; but even when these are used the patient should be ordered to drink at least one quart of water daily, pref- erably a mineral water, to promote 728 ANIMAL EXTRACTS (SAJOUS). flushing of the ki(hiey and thus facil- itate the elimination of toxic wastes and detritus. One or 2 grains of desic- cated thyroid three times daily usually suffice, but 3 grains can be given if no rise of temperature is observed. Case of multiple carcinoma of the skin and subcutaneous tissue in a widow aged 61. The original growth had been removed a year before the author saw the patient, but other growths had since appeared, and the patient's health was declining. Thy- roid medication was tried, starting with 5 grains daily, gradually in creasing to 10 grains, and finally to 15 grains, daily. The patient quickly showed signs of improvement; the palpitation, sickness, and emaciation gradually disappeared pari passu with the gradual disappearance of the growths. In less than three months the growths had entirely disappeared, the patient was practically well, and had recovered her lost weight of 3 stone. This occurred in 1901, and at present the patient is still well and has not suflfered since. The writer summarizes other and similar cases from medical literature. E. Hughes Jones (Brit. Med. Jour., Feb. 25, 1911). Case of cancer of the larynx. The patient was a man 51 years of age who developed malignant disease of the larynx for which total extirpation of the larynx was done. After an attack of secondary hemorrhage the patient finally began to recover on the sixteenth day after the operation and gradual healing occurred. About three months later, a mass of glands over the right * carotid sheath were found to be second- arily affected, and these were removed. He kept well for eight or nine months after this operation, and then recurrence of the growth took place and a lump as large as a walnut developed on the right side of the neck. An attempt was made to remove it, but it was found at the operation that the growth involved not only the common carotid artery, but the prevertebral muscles. Complete re- moval could be accomplished only by exposing a healthy portion of the com- mon carotid, ligating it, and dissecting the cancerous mass up from below and sacrificing the pneumogastric nerve, an operation that would almost certainly have been fatal, while it gave little or no prospect of eradicating the disease. The lower portion of the mass involved the thyroid gland. Accordingly, the operation was abandoned except that a small portion was removed for micro- scopic examination. This proved to be cancerous. A few days later, the pa- tient was seen on consultation with Sir Charles Ball, who suggested that thy- roid extract should be given and cited 2 cases of inoperable cancerous lym- phatic glands in which that remedy had been tried with success. Three-grain doses of the extract were prescribed three times daily. ."Xt the end of four months' treatment, there was distinct diminution in size of the glands. The thyroid extract was continued with the result that the growth finally disap- peared completely, and the patient be- came quite well. There is now a series of well-authen- ticated cases of cancerous recurrences on lymphatic glands cured by thyroid extract. R. H. Woods (London Letter, N. Y. Med. Jour., July 22. 1911). The other agents indicated as such as would be warranted were the same general symptoms met in other disor- ders. The anemia, which, with the gen- eral vasodilation and the resulting re- cession of blood from the surface, gives the patient the waxy pallor some- times observed, should be met by iron, preferably Blaud's pill, and strychnine in full doses. In personal cases, by treatment based on general principles, using thyroid only when the growths seemed to take a fresh start, they have been kept in abeyance several years, six years in one case, four years in another. The same treatment is indicated in cases after operation to prevent recur- ANIMAL EXTRACTS (SAJOUS). 729 rence, the aim here being to enhance the functional activity of all organs, in- cluding those which govern the im- munizing processes. General tonics, especially iron and strychnine, and out- of-door life are of especial value in this connection. Cutaneous Disorders. — After a pro- longed trial of thyroid preparation in many diseases of the skin, dermatol- ogists have come to the conclusion that they were indicated in disorders due to deficient metabolism. As re- cently stated by Winfield, these in- clude the erythematobulbous type, which includes dermatitis herpetifor- mis, and the psoroeczematous type, to which belong prurigo, psoriasis, and chronic eczema. This is fully accounted for by the action of thyroid products on oxidation and metabolism I have described. This is well shown in the effects noted by Don: 1. Increased nutrition of the skin ; hence its probable remedial action in ichthyotic conditions : an effect pro- duced without any necessary abnormal perspiration. 2. Increased action of the cutaneous glands, accelerating excre- tion of waste products, thus keeping the surface in a supple condition. 3. Regrowth of hair, as shown in myx- edema and some cases of general alo- pecia. 4. Increased activity of the epi- dermal layers, causing desquamation of unJiealthy epidermis and reproduc- tion of a new covering, as observed in ichthyosis, psoriasis, dry chronic ec- zema, and also in some cases of myx- edema and cretinism. Series of consecutive cases of eczema in young children successfully- treated bj' thyroid. In the first case, 14 months old, the baby had suflfered from eczema of the face for nearly a year. This had been entirely re- sistant to the usual applications and internal treatment, nor was hospital treatment more efficacious. Two and a half grains of a thyroid tablet were given daily. In a little more than one month the child was entirely well. His cure persisted for nearly a month, when the disease showed a tendency to recur. The second course of thj'- roid was followed by a permanent cure. The 4 other cases gave similar results. Eason (Scottish Med. and Surg. Jour., May, 1908). Two cases of eczematous seborrhea successfully treated with thyroid. In the first case the scalp was normal at the end of two weeks; in the second in one month. Complete cure occurred in both cases, and has persisted. Mous- sous (Archives de med. des enfants, March, 1908). It is pretty certainly established that preparations from certain ductless glands exert a marked influence upon those dermatoses due to faulty metab- oJism. There is a certain class of skin diseases, those belonging to the ery- thematobullous tj-pe and those of the psoroeczematous variety, in which the preparations coming under the head of animal therapy seem to do the most good. J. M. Winfield (Interstate Med. Jour., Nov., 1909). In psoriasis thyroid is harmful when the eruption is developing, but it sometimes acts with surprising effi- cacy in fully developed cases. The un- toward effects observed by dermatolo- gists, however, are in great part due to the fact that they use too large doses. These, as previously stated, enhance catabolism violently and increase the waste products in the blood and, there- fore, the cutaneous disorder. The writer treated 9 cases in this way, i.e., by the administration of thyroid extract alone. In 3 it re- moved all traces of the disease. One of the relieved cases had proven in- tractable to the orthodox methods of treatment, by arsenic, chrysarobin, etc. The other 2 patients presented typical pictures of an average case of 730 ANIMAL EXTRACTS (SAJOUS). psoriasis. In 3 of the cases thus treated the lesions retrogressed markedly, but never entirely disap- peared. In the remaining 2 the treat- ment had no appreciable effect. It was administered on the basis of its favorable influence on metabolism. J. E. Hays (Miss. Valley Med. Jour., Jan., 1918). Sajous states that a perfect secre- tion of the thyroid is necessary for, 1, proper relationship of the amount of fat to the rest of the body; 2, proper nitrogenous metabolism of the body: 3, proper health and functions of the skin and its appendages, hair, nails, etc. Hence, deficient secretion is apt to produce disturbances of skin functions and to interfere with the metabolism of proteins and fats. The skin being the largest fat organ in the body, therefore bears the brunt of the manifestations occurring in deficient thyroid secretion. It must therefore be conceivable that changes in the hormone producing organs, re- sulting in disorders of general nutri- tion as above mentioned, may influ- ence the evolution of such skin mani- festations as dermatoses and eczemas. In considering the treatment, it must be borne in mind that a child with deficient thyroid secretion has lessened metabolic powers; Magnus Levy, DuBois, and Talbout, who have experimented with metabolism of cretins, found it to be very much less than normal. Talbout found that the metabolism of a cretin 2y2 years old was about equal to a normal child 8 months old. This means that we must give less food to these children at the beginning of treatment and in- crease the food with the improve- ment. Fairly large doses of thyroid should be administered at first, in order to remove results which have been pro- duced by privation of thj^roid secre- tion. Later, smaller doses are given to maintain a normal equilibrium and prevent a recurrence. Following im- provement, the dose of tlu'roid which at first was sufficient later becomes an overdose, according to the writer. increasing the oxygenizing process, and the patient begins to consume his own fat. Thyroid, therefore, should only be given when definitely indicated. If the lesions of the skin are re- garded as merely a symptom rather than a disease, greater progress will be made. In every obstinate skin manifestation, a thorough physical and chemical examination of secre- tions and excretions is indispensable for determining the proper method of treatment. The clinical picture of disturbances of internal secretions should always bq kept in mind, for it is very impor- tant that they should always be esti- mated in connection with any other symptom, since upon the proper treat- ment of this factor usually depends success or failure. M. H. Edelman (\. Y. Medical Jour., Mar. 9, 1918). Thyroid has been tried in lupus by a number of observers. Though the results were contradictory, the bulk of the evidence indicates that it is worthy of further trial. Owing to its inrtuence on oxidation, thyroid en- hances the nutrition of the skin and thus antagonizes the destructive proc- ess while promoting that of repair. As full doses have to be used during a prolonged period, the patient should be carefully watched. Thyroid has been tried in leprosy, but the results were not encouraging, though the remedy was pushed as far as safety would allow. In a case of hypertrophic rosacea which has resisted all forms of treat- ment, Isadore Dyer, of New Orleans, used thyroid with, for local use, a salve containing resorcin ^ j ; rose water, oiv; lanolin, q. s. ad ^vj. After two months there was decided improvement, the skin being soft and normal to the touch and the color greatly improved. ANIMAL EXTRACTS (SAJOUS). 731 The patient was discharged cured after three months of thyroid medication. Exophthalmic Goiter or Graves's Disease. — The results of treatment by thyroid preparations are reviewed under the heading of Graves's Disease, in the fifth volume, the reader is re- ferred to that article. This applies also to Goiter, reviewed in full in the same volume. Hemophilia.— Thyroid preparations are extremely valuable in this dyscrasia, due to a deficiency of fibrin ferment in the blood. As this body, according to my researches, is mainly composed of the adrenal product, the increased functional activity of the adrenals pro- voked by thyroid preparations admin- istered increases the blood's asset. The coagulation time in hemophilia may be brought down from over ten minutes to three or four minutes in adults by 3-grain doses of the desiccated thyroid three times daily after meals. This is effective not only in the treatment of the disease, but also when operations are necessary in hemophilics. Even such operations as removal of a kidney have been resorted to with perfect safety after the coagulation time had been reduced to three minutes. Case in which hemophilic epistaxis was absolutely unaffected by ordinary therapeutic agents, and the epistaxis became so persistent and exhausting that permanent blocking of the nasal fossa was necessary. Treatment by thyroid extract exerted an immediate and beneficial effect, and was fol- lowed by cure. In three days the violent and persistent epistaxis had practically stopped. In six days, about 8 grains of thyroid extract having been given daily, the purpuric eruption ceased. Scheffler (Arch, de med. et de pharm mil., March, 1901). Three cases of operations in "bleeders" in which the administra- tion of thyroid extract, for some days preceding operation, as advised by Sajous, was followed by remarkable results in lessening the hemorrhage at that time. Sajous holds that the thyroid extract stimulates the ante- rior pituitary body, which in turn excites the adrenals to greater activ- ity, thus augmenting the proportion of fibrin ferment in the blood, and consequently its coagulating power. This explains the action in these hemophilics, and its use is recom- mended as a preparatory treatment whenever surgical operation is to be undertaken in such persons. W. J. Taylor (Monthly Cyclo. of Pract. Med., July, 1905). Incontinence of Urine. — in a large number of these cases, the enuresis is due to general asthenia, and the mus- cular debility which attends this state carries along with it inability of the sphincters to perform their functions at all times, especially when during sleep general relaxation prevails. The influence of thyroid on general me- tabolism and nutrition and the result- ing increase of functional power in all organs affect equally both the cystic and urethral sphincters and thus overcome the trouble. The doses should be small in order to enhance general nutrition. Infectious Diseases. — So far thy- roid preparations have not been used to any marked extent in this class of disorders, but it is probable that they will eventually prove of great value owine to the identitv of the thyroid secretion as opsonin, pointed out by myself in 1907, as previously stated. Several investigators, including Marbe. of the Pasteur Institute, have since found that the administration of thy- roid preparations to animals increased the opsonic power of the blood. The enlargement of the thyroid, 732 ANIMAL EXTRACTS (SAJOUS). which can be distinctly detected by palpation, and its erethism during in- fectious and other toxemias indicate that it fulfills active functions in the immunizing process. [The participation of the thyroid in gen- eral immunity pointed out by myself in 1903 and since confirmed, we have seen, explains the overactivity of the thyroid in certain disorders. But, as I have re- peatedly emphasized in "Internal Secre- tions," vol. ii, this applies only to those diseases which are capable through their to.xins of exciting the thyroadrenal center, thus evoking a protective reaction on the part of the thyroid and adrenals. Various toxins and poisons are not only unable to excite this center, but can depress it. Hence the fact that in the conditions men- tioned (excepting septicemia, in which Vincent is wrong in his generalization) tlie thyroid gives no evidence, through tumefaction and tenderness, of overactiv- ity. C. E. DE M. S.] So far, thyroid preparations have been used in but few diseases. In true infectious tonsillitis, desiccated thyroid clears the field promptly. It does so, of course, by enhancing the bactericidal and antitoxic powers of the blood and glandular secretions. The bacteria being rendered more sensitive, that is to say. more easily 'digestible, they readily become the prey of the phagocytes, which are ex- tremely numerous in the tonsils. Thyroid gland has also been em- ployed advantageously in septicemia and in recurrent erysipelas, i.e., in streptococcic infection. Pulmonary tuberculosis, before the disease is sufftciently advanced to compromise the mechanism of respi- ration, that is to say, during the first or incipient stage, is especially vul- nerable to the action of small doses of thyroid. As I urged in 1907, the tubercle bacillus, which is also patho- genic when dead, owes its morbid ac- tion to an endotoxin rich in phos- phorus ; being thus prone to oxidation, vvliile the blood's oxidizing power is enhanced simultaneously, this bacil- lus is promptly destroyed. The daily administration of thyroid gland at a time corresponding to or preceding infection with tuberculosis, and in such doses as are well borne, causes an energetic acceleration of the metabolism of the organism and modifies favorably the action of the experimental tuberculous and pseudo- tuberculous infection in rabbits. The animals treated with thyroid gland live longer than the control animals, and in some cases life is prolonged indefinitely. Frugoni and Grixoni (Berl. klin. Woch., June 21, 1909). As stated above, it is only in the incipient stage that, as shown by per- sonal experience, thyroid gland is useful to check the morbid process. Later, it produces exhaustion owing to the excessive catabolism it awak- ens, even in very small doses. Insanity. — The idiocy of cretinism and the wonderful improvement that thyroid preparations bring about in young cretins suggest that a direct re- lationship must exist between the func- tion of the thyroid and the organ of mind, the brain. The functions I have ascribed to the thyroid to increase the vulnerability of phosphorus-laden cells, etc.. to oxidation explain this beneficial action. Briefly, the thyroid preparation raises the ability of the cerebral cells to replace the sluggish metabolism and inadequate nutrition of which it has been the seat to the level of normal me- tabolism and nutrition. In other words, the cerebral cells, along with those of the entire organism, are caused to burn faster ; the vital process being cor- respondingly more active, the function of the brain, as the seat of mental proc- ANIMAL EXTRACTS (SAJOUS). 72>?> esses, is sooner or later in young^ sul)- jects carried on with adequate vigor. Such being the case, we can only ex- pect benefit when increased metabo- lism and cell nutrition is required, i.e., in stuporous melancholias due to de- fective nutrition, depressive states in general, when organic lesions are not present. Again, in view of the prop- erty thyroid preparations possess of promoting the proteolysis or breaking down of waste products we should ex- pect benefit in puerperal and climac- teric insanities. Clinical observation has sustained this interpretation. As a rule, however, psychiatrists have used entirely too large doses ; hence the untoward efifects recorded. Lactation. — Thyroid preparations have been recommended as galacta- gogues by Hertoghe, Cheron, and oth- ers. In some cases on record the secre- tion of milk was free as long as thyroid was taken and failed as soon as it was neglected. This is obviously due to its stimulating influence on general oxida- tion, all functions being enhanced. Middle-ear Disorders. — Thyroid preparations have been tried in several of these disorders, sclerosis, middle-ear catarrh, ossicular sclerosis, etc., but the results, on the whole, were not encour- aging. They should be tried, however, in suppurative processes associated with general adynamia, as these often persist merely because the bactericidal and antitoxic powers of the blood are deficient. Thyroid, by enhancing these protective functions, has at least proven valuable in ulcerative disorders located elsewhere, even when osseous tissue was involved, as in osteomyelitis. Nervous Disorders. — Epilepsy. — This disease is sometimes greatly bene- fited by the use of thyroid prepara- tions, but only when small doses are used. Untoward results are readily caused by excessive dosage, as shown by loss of weight. Coincidently, meat should be removed from the diet, and the patient ordered to drink copiously of water. The spasmogenic wastes are thus increasingly broken down by the thyroid; they are formed less freely owing to the abstraction of meat, and the end products of metabolism are more readily eliminated by the kidneys owing to the free use of water. I have observed excellent results through this treatment. It must not be forgot- ten, however, that other factors — intestinal worms, indigestible foods, scars, dentition, alcohol, lead poison- ing, syphilis, nasal growths, dental interpressure, and phimoses — may pro- duce epilepsy, and that the cause must be removed in such cases if a satisfac- tory result is to be obtained. A conclusion forces itself upon us, viz., that idiopathic epilepsy is alwaj-s associated with defective metabolic processes. The latter may originate from many sources. There is a cer- tain class of epileptics whose seiz- ures are in direct relationship with a disturbed function of the ductless glands and particularly the thyroid. In such cases the reason for failure of the usual treatment lies in the want of thyroid feeding. Administration of the latter will be of great benefit. Six illustrative cases. Alfred Gordon (Penna. Med. Jour., July, 1908). Three cases of epilepsy in which the simplifying influence of Dr. Sajous's discoveries as to the func- tions of the ductless glands and other body structures is clearly shown by good results. All three being due to the retention of excrementitious sub- stances in the blood, and the irritat- ing action of these poisons upon the spasmogenic centers — the indications, of course, were to destroy these poisons. Drugs known to do so by increasing the antitoxic substances through the ductless glands — mer- 734 ANIMAL EXTRACTS (SAJOUS). cury and desiccated thyroid — were administered. To assist this antitoxic process of the osmotic properties of the blood, physiological saline solu- tion was given as beverage. On the other hand, the sources of intoxica- tion were as much as possible elimi- nated by purgation and dietetic meas- ures calculated to prevent the accu- mulation in the blood-stream of any toxic wastes, i.e., wastes imperfectly prepared for prompt elimination by the kidneys. J. Madison Taylor (Monthly Cyclo. of Pract. Med., March, 1909). When epilepsy is complicated by bromism this may be coml)ated with thyroid gland. A cachet 0.1 Gm. (1^ grains) of desiccated thyroid is given every morning for three weeks, then suspended from time to time for a fortnight. Two doses, each of 1 Gm. (15 grains) of potassium bro- mide, are given daily at equal inter- vals, say at 10 a.m. and 10 p.m., apart from meals, and dissolved in half a wineglassful or less of water. The bromide is to be given regularly with- out suspending the treatment. J. A. Sicard (Jour, de med. de Paris, Nov. 19, 1910). Two cases of cretinism in twin brothers, l)oth of whom suffered in addition, one from epileptic seizures, the other from a marked degree of ataxia. The epileptic attacks began at the age of 23 and rapidly increased in frequency until they were of al- most daily occurrence; there were occasional attacks of petit mal be- sides the seizures of grand iiial. The attacks were greatly modified by thy- roid therapy, although this patient could not tolerate more than 25 grains of the extract daily. The other twin, when 14 years old, de- veloped a staggering gait, walking like a drunken man, and suffering severe pains about the hips; the arms soon became involved so that he could hardly write. This patient be- gan by taking 15 grains of thyroid extract a day, and the dose was in- creased gradually until he was taking 45 grains a day without toxic mani- festations. All his symptoms im- proved, including the ataxia; he is able to walk (though with a wad- dling movement) and to write, earn- ing his living by typewriting. L. S. Manson (Med. Record, Jan. 1, 1910). A considerable number of cases of epilepsy present symptoms of endo- crine disorder which stand out more or less prominently. The administra- tion of thyroid gland was found in some instances to have true therapeu- tic value. H. H. Drysdale (Ohio State Med. Jour., xii. 802, 1916). In some cases of epilepsy the ad- ministration of small doses of thyroid gland (Vs to % grain— 0.008 to 0.016 Gm. — three times a day) for long periods seemed to raise the patient's physiological level with marked bene- fit, thus permitting them to respond more favoral)ly to other treatment. The diet should be so modified that the organism, already toxic, should be put to as little strain as possible, especially the liver, thyroid and other defensive glands. F. X. Dercum (Jour. Amer. Med. Assoc, Ixvii, 247, 1916). In cases of combination of epilepsy and tetany one has to examine care- fully, whether the cause of these dis- eases is an insufficiency of the thy- roid and parathyroid glands. Only in this case were very good results ob- tained from rectal applications of fresh thyroid and parathyroid glands at tile same time. In other cases. however, not due to insufficiency of the thyroid-parathyroid system no effect can be expected from this treatment. G. C. Bolten (Genees- kundige Bladen, Haarlem, xix, 301, 1917). Eclampsia. — It is now generally rec- ognized that this complication of the puerperal state is due to toxemia. Thy- roid extract is indicated, therefore, since it enhances the destruction of toxic wastes and other poisons. This accounts, from my viewpoint, for the fact that a number of cases have been reported in which the con- ANIMAL EXTRACTS (SAJOUS). 735 vulsions ceased under the influence of single grain daily. The free use of rather large doses of thyroid gland, water as beverage, abstention from red Nicholson obtained excellent results meats, and out-of-door exercise are with 7y2 grains of thyroid extract every necessary accompaniments to obtain three or four hours, with morphine as the best results. an adjunct. Baldowsky confirmed its Asthma. — A certain proportion of value in 2 cases; in the first, a multi- these cases is also, as is well known, a para in the seventh month of preg- manifestation of the gouty diathesis, nancy, a convulsion occurring, 18 grains Hence, the value of thyroid prepara- of thyroid extract were given. The fits tions owing to the antitoxic action ceased. The thyroid was continued for which renders them useful in migraine, two days longer — 10 grains daily — and Tetanus. — As thyroid preparations the patient seemed quite recovered. A promptly arrest the tetanus that occurs fortnight later she again developed se- after removal of the thyroid, they vere eclamptic fits, sixteen seizures al- suggest themselves not only as pro- together, which were treated by thy- phylactics, but also to assist teta- roid extract, with narcotic remedies, nus antitoxin. The latter sometimes and recovery followed. The other was fails merely because the spasmogenic a primipara at term who was suddenly poisons are not sensitized or "opso- seized with convulsions at the com- nized" to its effects, as shown by a com- mencement of labor. Thyroid extract paratively low temperature ; desiccated alone was given, and the attack ceased thyroid in full doses tends to correct before the rupture of the membranes, this condition and to increase the The labor took place without any un- chances of recovery, usual symptom, and the puerperium Osseous Disorders. — As far back as was normal. 1897 Gabriel Gauthier showed that I have pointed out, however, that the delayed union in fractures was coun- action of the thyroid is greatly enhanced teracted by thyroid preparations, con- by the simultaneous use of hypodermo- solidation occurring in some instances clysis. In some cases the thyroid as early as the fifteenth day. Similar preparation was dissolved in the saline results have been obtained by many solution injected. observers, the proportion of success- Migraine. — This disorder is now ful cases being about 60 per cent, generally attributed to the gouty diath- Removal of the thyroid had been esis, i.e., to the accumulation in the found by Hanan, Steinlein, and Bayon blood of intermediate waste products to prevent the healing of fractures in of the purin or alloxuric type. Thy- otherwise healthy animals, thus af- roid preparations, by promoting the fording a sound basis for the use of conversion of these toxic products into thyroid preparation. Its beneficial bodies that are readily eliminated by effects are best shown in the young, the kidneys, antagonize this pathogenic its value decreasing as the patient is process. But here, again, small doses more advanced. are alone indicated; 1 or 2 grains (0.6 Thyroid preparations have also been to 0.13 Gm.) of desiccated thyroid used with success in osteomalacia, during meals suffice at first, the effect rickets, and osteomyelitis. All these being kept up after a few weeks by a beneficial effects are explained by the 736 ANIMAL EXTRACTS (SAJOUS). influence of thyroid on metabolism, all functions, including the processes of repair, being enhanced. The marked influence of the thyroid over calcium metabolism shown by Parhon. Macal- lum, and others is another potent factor in the marked benefit noted in these disorders. Rheumatism, Chronic Progressive. — Following the experience of Revil- liod, Lancereaux has urged the value of thyroid preparations in this class of disorders many years, but, as is often the case, the scoffers of the profession have caused the valuable observations of both these distinguished clinicians to be ignored, thus perpetuating need- lessly the acute sufferings of the many victims of this disease. When its path- ogenesis is interpreted from my stand- point (see "Internal Secretions" Suppl., p. 1869, 1907), i.e., "inadequate catabo- lism of tissue wastes and excitation by the toxic products formed of the vaso- motor center," the favorable influence of thyroid preparations is self-evident: the toxic wastes which provoke excess- ive vascular tension and pain being more actively broken down, the pri- mary cause of the disorder is removed. Souques (1908), in 2 cases of this dis- ease, found the thyroid gland atro- phied. Many cases have recently been treated successfully. Leopold-Levi and de Rothschild, who have had the great- est experience with this class of cases, recommend— in keeping with the teach- ings of my own experience, and now sustained by the experience of many other clinicians — that small doses should be used. [As Rachford observed over twenty years ago "thyroid feeding will increase the excretion of the alloxuric bodies in the urine, and will produce an acute ar- thritis in a patient suffering from chronic rheumatic gout." Large doses will thus prove harmful where small doses will prove beneficial. C. E. de M. S.] Case of a man who had suffered for thirty-six years from rheumatism and gout, with decided arterioscle- rosis, high-tension pulse, heart hy- pertrophied, and albuminuria, who under the influence of Baumann's iodothyrin, started with K' Gm. daily —increasing % Cm.— was relieved of the pain in the limbs, polyuria and albuminuria controlled, the heart im- proved, tension of the pulse lessened, although it was more rapid. Lance- reaux and Paulesco ( Bulletin de I'Acad. de Med.. Jan. 3, 1899). Uterine Disorders. — Various con- ditions of the genital apparatus, such as the onset of puberty, pregnancy, fibroid tumor, which cause a distinct change in the metabolism of the entire organism, frequently produce enlarge- ment of the thyroid gland. Again, the deficiency of the normal thyroid secretion following thyroidectomy in myxedema, cretinism, etc., is often associated with atrophic changes in the genital apparatus, as shown by Fisher, of \'ienna This clearly indicates direct associa- tion between the thyroid and the genital system, and has suggested the use of thyroid preparations. The vomiting of pregnancy is also benefited by their use. They have been found of value for the purpose of arresting hemorrhage, whether this occur in connection with abortion, tumors, or uterine malposi- tions. A remarkable case of metror- rhagia due to hemophilia successfully treated with thyroid extract was re- ported by Dejace. In the disorders of menopause, hemorrhages, flushes, irritability, migraine, etc., thyroid preparations are of undoubted value owing to their ability to promote the ANIMAL EXTRACTS (SAJOUS). 7Z7 destruction of waste products, which eral nutrition of all tissues, including underlie these morbid phenomena. It is very probable that the toxemia of pregnancy is largely dependent upon faulty metabolism; at least, an insufficient metabolism is an accom- paniment which greatly adds to the seriousness of the condition. Failure of the thyroid gland to hypertrophy the bones, as shown by its action in cretinism, myxedema, and kindred disorders — osteomalacia, rickets, and osteomyelitis. 3. In disorders due to lowered nutri- tion of the muscular elements, includinsf the skeletal and vascular muscles, as during pregnancy is probably fol- shown by its action in general adyna- mia, neurasthenia, and myasthenia. 4. In all cases in which the processes of repair or absorption are deficient, as shown by its action in delayed union of fractures, certain benign and ma- lignant neoplasms, and syphilitic tis- sue and bone necrosis. 5. In infectious diseases — owing to the increase of autoantitoxin, thyro- prove a faulty metabolism and thus JoJase (opsonin), and phagocytes— as give a favorable influence upon the , -u -^ ^- ■ ^ ■, • • r , ^- r ^, ^^^ ■ ^r sfiowu bv its actiou m tuberculosis, manifestations of the toxemia of - ' typhoid fever, infectious tonsillitis, certain exanthemata, and, in general, infections in which fever is a prom- inent symptom. lowed by insufficient metabolism, and may result in the various forms of toxemia of pregnancy. When there is a failure of the normal hyper- trophy of the thj'roid gland during pregnancy and when there is a dis- eased thyroid, as in Graves's disease, the administration of thyroid sub- stance, by supplying the deficiency of the normal thyroid secretion and by diuretic action, may materially im- pregnancy. Ward (Surg., Gynec. and Obstet., Dec, 1909). The writer observed 6 cases of uterine hemorrhage in which no pel- vic disease was discernible, which yielded to treatment with thyroid gland. Salzmann (Amer. Jour. Ob- stet., vol. Ixxiv, 812, 1916). PARATHYROID ORGANO- THERAPY. The two internal of these four small Summary. — Thyroid preparations granules were described, as previously have been used and recommended in stated, by Sandstrom in 1880, while the many other diseases, but the fore- two external were discovered by Nich- going seem to me to represent those olas in 1893, and also in 1895 by Kohn. in which they are productive of real Though distinct from the thyroid good. My own experience has sug- gland, they are in close apposition to, gested that this would prove true, and sometimes imbedded in, this organ, particularly as to desiccated thy- and are supplied mainly by the inferior roid : — thyroid artery. Though histologically 1. In diseases due to slowed de- different from the thyroid gland, they struction of toxic wastes, as shown also contain a colloid substance in by its action in tetany, epilepsy, which iodine occurs in relatively large eclampsia, disorders of menopause, proportion. That -they carry on some asthma, chronic rheumatism, mi- general function is shown by the fact graine, and also by those due to slow that their removal causes tetany, while oxidation of fats, as in obesity and removal of the thyroid divested of its Dercum's disease: adiposis dolorosa, parathyroids causes myxedema, arrests growth, and impairs calcium metabo- 2. In diseases due to lowered gen- 1-47 738 ANIMAL EXTRACTS (SAJOUS). lism, the bones, including the teeth, be- coming soft and brittle. The functions of the parathyroids are still in doubt; some investigators claim that they have no independent function; others that they govern cal- cium metabolism independently of the thyroid. A third group, to which my own researches have caused me to be- long, believe that they supply a secre- tion which combines with that of the thyroid to carry on the functions of the latter, i.e., to sustain tissue and calcium metabolism besides carrying on their antitoxic functions. From my view- point their secretion plays the principal role in the formation of Wright's op- sonin in conjunction with the thy- roid, as shown under the preceding heading. [The investigations of King, Biondi (Berl. klin. Woch., XXV, p. 954, 1888), Zielinska (Virchow's Archiv, cxxxvi, p. 170, 1894), Vassale and de Brazza (Arch. ital. di biol- ogia, xxiii, p. 292, 1895) on the thyroid, and those of Welsh (Jour, of Anat. and Physiol., April, 1898), and Capobianco and Mazziato (Giorn. Int. de Scienze, Nos. 8. 9, and 10, 1899), and others on the parathyroids, have shown that the product of these organs passes into perivascular lymph-spaces. Being then transferred to the larger cervical lym- phatics, they are discharged by the right and left lymphatic ducts— the thoracic duct, ac- cording to Pembrey (Hill's "Recent Ad- vances in Physiology," p. 579)— into the sub- clavian veins, and by way of the superior vena cava to the heart. Here they become merged with the venous blood of the entire organism, forming a single secretion — in accord with Gley's (La Presse niedicale, January 12, 1898) view— which is then in- evitably carried to the heart, and thence to the lungs. As the venous blood carrying the secretion passes to these organs to be oxy- genized, the secretion itself is likewise car- ried to the air-cells. The purpose of this itinerary suggests itself when we recall that, as stated by Noth- nagel and Rossbach (Therapeutique, p. 261, 1889), hemoglobin can fix large quantities of iodine. It accounts also for the fact that Gley (La Semaine medicale. May 25, 1898) and Bourcet found iodine in the red corpus- cles. Being a component of the albuminous hemoglobin of these cells with adrenoxidase, however, iodine should be found in all tis- sues. While Bourcet (cited by Morat and Doyon, Traite de physiologic, vol. i, p. 470, 1904) ascertained that such was the case, Justus (Virchow's Archiv, clxxvi, p. 1, 1904) found it in all cellular nuclei. This latter feature is important, since, as we have seen, iodine serves to increase the inflammability, as it were, of the phosphorus which ail nuclei contain. C. E. de M. S.] THERAPEUTICS.— The actual value of parathyroid in therapeutics has not as yet been clearly deter- mined. It has been tried with benefit in postoperative tetany by several clinicians. MacCallum found large quantities injected intravenously nec- essary. Vassale, James, and Halsted have also had favorable results. While Birch found thyroid ineffectual, para- thyroid caused recovery. The nucleoproteid of the parathyroid relieves the symptoms of acute tetany in dogs, but the globulin has no such power. Boiling or heating the nucleo- proteid solution at 80° C. for half an hour destroys its activity, and it de- teriorates rapidl}^ when kept in solu- tion or frozen. The nucleoproteid relieves tetanj' by the mouth, but more effectively when given subcu- taneously or intraperitoneally. Berk- eley and Beelie (Jour. Med. Re- search, Feb., 1909). Three cases found in literature and 1 personal case in which the transplantation of human parathy- roids was followed by recovery. Danielson (Beitrage z. klin. Chir., Bd. xxxvii, S. 998, 1910). In postoperative parathyroid tetany — which is prevented by removing only, as does Kocher, the central part of the thyroid, thus leaving intact the posterior capsule, to which the para- ANIMAL EXTRACTS (SAJOUS). 739 thyroids adhere — the spasms may be arrested bv implanting hum;m thyroids from persons who have just died of some non-infectious disease. Implanted glands do not act at once; it is only when they assume their normal func- tions in situ that recovery occurs. Study undertaken with a view to determine the course to be pursued by the surgeon when a parathyroid gland has been accidentally removed or deprived of its blood supply, and in the hope that it might be attended with such success as to justify the attempt to transplant this glandule from man to man. The transplanta- tions were made either into the thy- roid, the spleen, or in or behind the rectus muscle of the abdomen, and were both auto- and iso- transplanta- tions. The writer's deductions were as follows: — 1. The autotransplantation of para- thyroid glandules into the thyroid gland and behind the musculus rec- tus abdominis has been successful in 61 per cent, of the cases in which a deficiency greater than one-half has been created. 2. In no instance has the auto- transplantation succeeded without the creation of such a deficiency. 3. Isotransplantation has been uni- formly unsuccessful. 4. Parathyroid tissue transplanted in excess of what is urgently re- quired by the organism has not lived. 5. One parathyroid autograft may suffice to maintain the animal in good health and spirits for many months and possibly for years. 6. Excised or deprived of their blood supply in the course of opera- tion upon the human subject, para- thyroid glands should, in the present State of our knowledge, be grafted, and probably into the thyroid gland. 7. Complete excision of the thyroid lobes in dogs may be well borne for a year or more. The myxedema, which usually has manifested itself within a few weeks, has not increased after the first few months. May it subseciuently diminish with the hy- pertrophy of accessory thyroids? 8. Parathyroid tissue is essential to the life of dogs, as has been conclu- sively proven by the result of ex- cision of the sole sustaining graft. W. S. Halsted (Jour, of Exper. Med., vol. xi, Xo. 1. 1909). The indifference of some surgeons in respect to the importance of these parathyroids merits severe criticism. Personal case which, their advice be- ing followed, developed very severe tetany. The case was saved, only after all other measures had been tried in vain, by the implantation of a thyroid with its parathyroids, ob- tained from a small monkey and, one month later, of 3 parathyroids and a piece of thyroid the size of a small walnut, all obtained one-half hour after death from the body of a man who had died of Bright's disease and uremia. These tissues, placed at once in normal saline solution at 32° F. (0° C), were implanted success- fully within an hour, the simian thy- roid beneath the patient's sternomas- toid, and the human thyroid and parathyroid beneath her left rectus abdominis, under chloroform anes- thesia. \V. H. Brown (Annals of Surg.. March. 1911). An emulsion of fresh parathyroids may also arrest the spasms, but obvi- ously only as long as the injected emul- sion is active. It is administered in saline solution subcutaneously. It may prove curative, as in the case cited be- low, but here the parathyroids were only partly removed, the recovery be- ing eventually due to the resumption of. function by the latter. Case treated successfully by means of an emulsion of parathyroids given subcutaneously. Five fresh beef parathyroids were placed in a 1 : 1000 solution of bichloride of mercury and allowed to soak about ten minutes. The glands were cut, under strict asepsis, into 5 pieces under physio- 740 ANIMAL EXTRACTS (SAJOUS). logical salt solution. These pieces were placed in a mortar and ground into a homogeneous mass, 400 c.c. of sterile salt solution being poured into the mortar. This was then filtered and given as salt transfusion into the patient's breast. The oral use of thyroid and parathyroid extract and the feeding of raw parathyroids had proved entirely useless. Only 1 parathyroid had been entirely re- moved, and the 3 others only partly so. Branham (Amer. Jour. Med. Sci., vol. xlviii, p. 161. 1908). [In this case the injured parathyroids recovered and resumed their functions. The emulsion only served, therefore, to compensate for the temporary' absence of secretion following the partial destruc- tion of the tliree parathyroids and did not itself bring on recovery. C. E. de M. S.J Meat should not be given to such cases, since it increases the tetany. The diet should be limited to milk, farina- ceous foods, and fruit. Exercise is harmful by promoting the formation of spasmogenic waste products. Rest in bed or in an armchair tends to reduce the frequency and violence of the spasms. Vassale claims that the parathyroid extract relieves eclampsia as certainly as thyroid does myxedema, while Berkeley tried it with some degree of success in paralysis agitans. The lat- ter gives 5 to 8 glands i)er day. minced and eaten in a bread-and-butter sand- wich. The writer has treated in consulta- tion and in his own practice 60 cases of paralysis agitans with para- thyroid. Of these between 60 and 65 per cent, who have given the remedy a fair trial have spoken favorably of it and have continued the treatment. More than a dozen who began three or four years ago have greatly improved and are now only uncomfortable when they are without the medicine. The writer concludes that with such a percent- age of benefited cases as this there seems no longer any reasonable doubt of the etiological relation be- tween the disease and the remedy. One or 2 cases in the hands of medi- cal friends or correspondents appear to be almost cured, though of such a disease in a patient of advancing years a "cure" is always to be spoken of with reserve. Berkeley (Med. Record, Dec. 24, 1910). Simonine also speaks of encourag- ing results in Sydenham's chorea (5 cures), but the remedy has been tried by too few observers to warrant a con- clusion as to its actual value. ADRENAL OR SUPRARENAL ORGANOTHERAPY. JJrown-Sequard showed in 1856 that death followed removal of both adre- nals in from a few hours to three days after a series of general phenomena corresponding to those of Addison's disease, viz., steady decline of the blood- pressure, intense prostration, and mus- cular w^eakness. This observation was not only confirmed by many other in- vestigators, but Oliver and Schafer, Szymonowicz, and Cybulski showed that adrenal extract caused a marked, though ephemeral rise of the blood- pressure and increased the power of the cardiac contractions. This was at- tributed to a direct action on the mus- cular elements of the arterioles and on the cardiac muscle, all tissues inner- vated by the sympathetic system. On the whole the function of the adrenals was thought to contribute to the main- tenance of the normal blood-pressure and to sustain the tone of the tissues thus innervated. [Although the above is the view gen- erally taught concerning the role of the adrenals, physiologists themselves have recently reached the conclusion that it is erroneous. In a summary of the whole question in the April, 1917, number of ANIMAL EXTRACTS (SAJOUS). 741 "Endocrinology," Professor Swale Vin- cent concludes, for instance, that "we know nothing of the functions of the ad- renal body regarded as an organ on its own account." Not only is the blood- pressure theory of Oliver and Schaefer shown to be fallacious by recent experi- ments, but the antitoxic theory of Abel- ous and Langlois in virtue of which cer- tain toxic substances are destroyed by the adrenals likewise. "It must be confessed,'' writes Vincent in this connection, "that the antitoxic theory has not been sub- stantiated." As is well known, I have attributed en- tirely different functions to the adrenals since 1903. As shown below, these have been experimentally and clinically sus- tained. C. E. DE M. S.] The investigations of Young and Lehmann, Austmann and Halliday, Moore and the more recent observa- tions of Hoskins and McClure, among others, have shown, however, that it is not the function of the adrenals to maintain the blood-pressure, since the amount of their secretion poured into the adrenal veins tends to lower it. When, however, the blood-pressure is morbidly reduced, adrenal extract, ad- renalin or any active principle, acting pharmacologically, w^ill tend to raise it. A quick rise in the blood-pressure of dogs was followed by a rapid fall and a secondary rise when adequate doses of adrenalin were administered intravenously (0.5 to 1 c.c. — 8 to 16 minims— of 1: 10,000). After study- ing- various hypotheses to account for this, the writers conclude that the primary rise is due entirely to peri- pheral action, and the secondary rise apparently to a central action of the adrenalin acting through the sym- pathetic ganglions. This central action can be prevented by pithing of the brain or removal of the head. McGuigan and Hyatt (Jour. Pharm. and Exper. Therap., Sept., 1918). To determine whether the dilator action of adrenalin was confined to carnivorous animals, the writers studied its action on the following species: snapping turtle, fowl, opos- sum, horse, goat, cats and dogs, fer- ret, raccoon, rats, rabbits and mon- keys. This extensive study led them to conclude that the usual vasomotor reaction in skeletal muscle was dila- tation with moderate doses of ad- renalin, except in the case of rodents; and because of the uniform occur- rence in other mammalian orders, as well as the presence in the monkey, it was believed that these mechanisms were also present in man. Hartmann, Kilborn and Lang (Endocrinology, Apr.-June, 1918). Ether anesthesia has a marked in- fluence in diminishing the pressor re- sponse to minute amounts of adre- nalin injected directly into the cir- culation. Hemorrhage also acts to lessen or abolish the response, and to a degree directly proportional to the lowering of the blood-pressure it causes. In the exsanguinated animal an amount of adrenalin 3 or 4 times that sufficient to produce a pressure rise of 10 to 15 mm. of mercury, under normal conditions, may be entirely without effect. The response to large doses, on the other hand, is uninflu- enced by ether or hemorrhage. These facts have a practical bearing not only on the employment of adrenalin to tide over collapse, but on its possible utilization in the future to raise a low, blood-pressure to the normal height and maintain it during a considerable period. The amount of adrenalin which under normal conditions will suffice to bring* up the blood-pressure may have little or no effect on an etherized individual or on one who has lost blood. Rous and Wilson (Jour, of Exper. Med.. Feb., 1919). Blum and other experimenters have found that adrenal extractives cause glycosuria by enhancing carbohydrate metabolism, while Josue has shown that they provoke arteriosclerosis, an observation confirmed by many investi- gators. 742 ANIMAL EXTRACTS (SAJOUS). The action of adrenal preparations is exercised upon involuntary muscles — those of the vessels, heart, intestines, and uterus, for example. But, accord- ing to the prevailing view, this action may be antagonistic; it may inhibit the action of the intestines, act as mydriatic and promote the secretory activity of the lachrymal and salivary glands. PHYSIOLOGICAL ACTION.— Personal researches, including a large number of experimental and clinical facts found in literature led me to the conclusion in 1903 that the physio- logical function of the adrenal secretion was (1) to take up the oxygen of the air in the pulmonary alveoli and carry this gas to the tissues as a constituent of the oxyhemoglobin, and (2) that it was the adrenal secretion which, as far as the role of oxygen in these processes is concerned, sustained oxidation and metabolism. Referring the reader to the article on "Adrenals, Diseases of," in this volume and to my work on the "Internal Secre- tions and the Principles of Medicine," the main factors determined by my investiga- tions were brief!}': (1) that the secretion of the adrenals has a marked affinity for oxygen, and that, owing to its passage into the inferior vena cava, it is inevitably carried to the pulmonary air-cells; (2) that once here it absorbs oxygen — thus fulfill- ing the role of a secretion deemed neces- sary by various physiologists (Paul Bert, Muller, Bohr, Haldane and Lorrain Smith, and others) to account for pulmonary respiration; (3) that it becomes, also in this location, the albuminous (96 per cent) constituent of hemoglobin and the red corpuscles, the identity and source of which physiologists have failed to identify, and (4) that this albuminous constituent of the hemoglobin which I have termed "adrenoxidase" owing to its source, the adrenals, and to its identity as oxidase, is distributed by the red corpuscles to all parts of the body as an oxidizing sub- stance. [The essential feature is whether the adrenal product can, as I have held, con- vert the hemoglobin of venous blood into the oxyhemoglobin of arterial blood. This has been sustained lately by Menten (Amer. Jour, of Physiol., vol. xliv, p. 176, 1917) who found that the addition of ad- renalin to diluted human venous blood caused an increase in the intensity of the oxyhemoglobin absorption bands. Kariya and Tauska (Jour. Tokyo Med. Assoc, vol. xxvi. No. 20, 1913) had already noticed in a study of hemolysis, that ad- renalin acted as hemoglobin when fixed from the red corpuscles. C. E. de M. S.j This interpretation explains the phe- nomena that attend the use of adrenal extracts, adrenalin, etc., in therapeutic doses. The rise of temperature noted by Morel, Lepine and the concomitant rise of temperature and increased me- tabolism noted by Oliver and Schafer are due to increased oxidation. It ex- plains also the rise of a low blood-pres- sure, since increased metabolic activity — excited directly by the adrenal prin- ciple besides that due to general oxidation — of the muscular coats of vessels is manifested by contraction, and, therefore, by elevation of the blood-pressure. The increased power of the heart is the obvious outcome of increased metabolism in the myocar- diuin, precisely as it is in the vascular muscles, while the slowing of its ac- tion is due to the greater diastolic ex- pansion that attends increased func- tional vigor and the greater resistance the blood-column offers as a result of the increased blood-pressure. The same process explains the phe- nomena produced by adrenal extract- ives which appear quite discordant from its more familiar effects on the blood-pressure, the heart, etc. They produce arteriosclerosis by causing ex- cessive contraction of the vasa vaso- rum, from which the arterioles receive ANIMAL EXTRACTS (SAJOUS). 743 their blood. The walls of the arteries these minute vessels nourish being partly or completely deprived of blood, they degenerate, and sclerosis follows. Glycosuria is also the result of excess- ive metabolism ; the pancreas, as are all other organs, being rendered over- active, its ferments are secreted in ex- cess. Amylopsin being one of these, the hepatic glycogen is converted into sugar in quantities exceeding the needs of the tissues, and the unused sugar is eliminated by the kidneys. Increased metabolism likewise explains the ab- normal activity of the lachrymal and salivary glands. Finally, the antagonistic effects of these agents are accounted for by the fact that, while the intestinal vessels are contracted through the excessive metabolic activity produced in their muscular coats, the intestines them- selves are relaxed because the volume of blood supplied to them is reduced by the undue constriction of their vessels. [The participation of the adrenal secre- tion in this phenomenon is shown by the fact that the supposed inhibitory action of the sympathetic on intestinal movements (which, as I have shown in "Internal Se- cretions," is merely an experimental phe- nomenon brought about by excessive con- striction of the intestinal vessels) is offset by severing the nerves to the adrenals. This fact, first observed by Jacobi (Arch, f. exper. Pathol., Bd. xxix, S. 171, 1892), proves, from my viewpoint, that two sources of vasoconstriction (manifested by elevation of the blood-pressure) must al- ways be taken into account: (1) that due to vasomotor nerves, and (2) that due to increased activity of the adrenals. It is by producing a similar constriction of the arterioles that opium and its analgesic alkaloids cause constipation and relieve pain- — according to my views. C. E. DE M. S.] Although the contention of physiol- ogists that the adrenals do not destroy poisons through their secretion, as be- lieved by Abelous and Langlois is war- ranted, the fact remains that in the light of my views the adrenals in- directly and in conjunction with other substances, take part in immuniz- ing processes. We have seen under the heading "Adrenals, Diseases of," the striking influence of adrenalin in terminal hypoadrenia. This is un- doubtedly due in port to the influence of the adrenal principle upon general oxidation ; this function taking part in all protective functions, while enhanc- ing the formation of antigens. The writer conducted experiments which tended to show that one of the functions of the adrenal glands was to assist by means of their internal secretion in counteracting pathological processes or products whicli might tend to produce an abnormal constriction of the bronchioles. D. E. Jackson (Jour. Pharmacol. and Exper. Therap., Sept., 1912). Adrenalin prevents absorption of poisons, in poisoning by non-corros- ive substances such as cyanide, strychnine, and aconite, and thus per- mits of the stomach being emptied or a suitable antidote administered. It should be given at once, followed by the antidote or the stomach-pump. Another small dose may be given to prevent absorption of any remaining poison. J. L. Jona (Brit. Med. Jour., Feb. 8, 1913). Experiments including the use of violent cardiac poisons, anagyrine and nicotine, showed that after the destruction of all central vasomotor connections, effects which could only be attributed to the adrenals. We must, therefore, recognize two classes of cardiac stimulants: those which act through the nervous system and those which act through the adrenals. This he regards as a new fact in our knowledge of the role of the ductless glands in their relations to poisons. Gley (C.-r. de I'Academie des Sci- ences, June 29, 1914). 744 ANIMAL EXTRACTS (SAJOUS). [Nothing of the above is new. I pointed out in 1903-1907 (Internal Secretions) that it was through the adrenals that digi- talis and other cardiants produced their tonic effects, and not as generally taught even now, by a direct action of the drug on the heart-muscle — an absurdity. I also urge that the toxic phenomena ob- served by Albanese, Langlois and others should be attributed to the participation of the adrenal secretion in a general im- munizing function. It is not as "antigen" that it acts, however, as believed by Hal- pern. C. E. DE M. S.] Intraperitoneal injections of ex- tracts of guinea-pig adrenals, bring about in some rabbits the formation of substances which exhibit a vaso- dilator property in frogs. The writer deems it justifiable to consider these substances as antibodies with ad- renalin as an antigen. Halpern (Archiv. f. exper. Pathol, u. Pharm., Oct., 1913). On the basis of extensive clinical experience the writer recommends that %o grain (0.001 Gm.) of ad- renalin be administered by hypo- dermoclysis in H or 1 pint (250 or 500 c.c.) of saline solution in general in- fections. Being absorbed slowly, its action is sustained. Josue (Paris Med., Dec. 4, 1915). Physiologists are now teaching that the adrenal products inhibit the func- tions of the stomach, but this effect is only observed in animals when doses which are not used in man are admin- istered. Extracts of suprarenal gland vigor- ously inhibit gastric secretion. These extracts all contain more or less ad- renalin and, therefore, it is presum- able that their effect is produced by intensification of the inhibitory func- tion which is ascribed to the (gas- tric) sympathetic. Adrenalin is not as active a gastric inhibitor as supra- renal proteins obtained from extracts of the whole gland. These supra- renal nucleoproteins contain only traces of epinephrin. Extracts of the pituitary gland also inhibit gastric secretion, but only about one-half as vigorously as do extracts of the sup- rarenal. Rogers, Ablahadian and Cornell (Amer. Jour, of Physiol., Feb. 1, 1919). Practical experience in many cases has shown that far from inhibiting the gastrointestinal canal, adrenalin pro- motes, even when given a long time, its functional activity. The soft and elastic arteries in chil- dren and the integrity of the cardio- vascular and other systems render adrenalin peculiarly effectual in pedi- atrics. It seems to have a general tonic and an antitoxic action as well as its direct vasoconstricting effect. Except in very urgent conditions, ad- ministration by the mouth is prefer- able. This is harmless while it avoids abrupt changes in the circulation. Its action is more protracted by the mouth, and it seems to stimulate the centers, possibly by way of the sym- pathetic system. The dose is from 10 to 30 drops of the 1 to 1000 solu- tion. A. Galvani (Rivista di Clin. Pediat., May, 1918). The writer has obtained good re- sults in dyspeptics with gastric atony by prescribing 8 to 10 drops of 1 ; 1000 adrenalin solution 1 hour before each of the 2 main meals, lunch and din- ner. The results consisted in a diminution or disappearance of post- prandial discomfort or sensation of weight, a diminution of splashing sounds, and cessation of pain. Pron (Presse med., June 10, 1918). Physiology of Local Action. — The local application of an adrenal prin- ciple, adrenalin, epinephrin, etc., causes such marked contraction of the vessels that their lumina, when applied over small vessels, may become obliterated, thus arresting totally the flow of blood. The tissues become very pale, there- fore, and even blanched. These effects, however, are of short duration. Mu- cous membranes are similarly affected; ANIMAL EXTRACTS (SAJOUS). 745 hence, the frequent use of adrenal ex- tractives on the nasal mucosa and the conjunctiva. The constrictive effect on the blood-vessels is due to a direct ac- tion on their muscular elements; ap- plied to the eye, adrenal extractives also produce contraction of its muscles. Hence, the dilatation of the pupil, the wide separation of the eyelids, and ap- parent protrusion of the eyeball. From my viewpoint, the contraction of the vessels produced by adrenalin and the resultant blanching are due to the in- creased metabolic activity it awakens temporarily in the vascular and other tissues to which it is applied. [The process does not differ from that which obtains in the blood. It is that of exaggerated oxidation in which the adren- alin, as I have pointed out, plays the part of a catalyzer. Poehl found that the ad- renal active principle was endowed with catalytic properties. This enables it to activate greatly the process of oxidation without being itself rapidly consumed — its action recalling that of a ferment. Jolles showed, moreover, that the catalytic activity of a given volume of blood cor- responded with the number of red cor- puscles it contained. These corpuscles being the carriers of hemoglobin, which, in turn, contains the adrenal principle, as T have shown, adrenalin, when applied to the tissues, acts as if a large amount of oxyhemoglobin had been concentrated upon it. C. E. DE M. S.] A simple intratracheal injection of a solution of adrenalin in a normally breathing rabbit was found by the writers to penetrate within a few seconds to the alveoli, chiefly those of the left lower lobe; absorption was rapid and well maintained, and the procedure could be repeated effect- ively a number of times. Absorption of adrenalin from the lung could also be obtained at a time when double the dose given intramuscularly ex- erted no blood-pressure efifect what- ever; it continued also after the de- velopment of pulmonary edema. Auer and Gates (Jour. Exper. Med., June, 1916). It has been taught that adrenalin produced an increase in blood-pres- sure, but if there was one thing ad- renalin does not do it is that. Ad- renalin produces a fall in blood-pres- sure generally, though not always. In the Officers' Reserve Corps at Plattsburg the speaker tested many young men in the pink of condition with adrenalin. Within half an hour practically all had a fall in blood-pres- sure. That corresponded with the latest physiological laboratory find- ings. Adrenalin does not produce constriction of all the blood-vessels, but a constriction of the blood-ves- sels of the abdominal cavity, and dila- tion of the muscles of the thigh, whereas a larger dose produces con- striction of the blood-vessels of the skin covering the thigh. If the con- strictors overcome the dilators, there is rise in the blood-pressure. Walter Timme (N. Y. Phys. Assoc; N. Y. Med. Jour., Feb. 15, 1919). PREPARATIONS AND DOSE.— The preparations most generally used are the dried adrenal gland, the siipra- renalmn siccum of the 1915 U. S. P., available in tablets or powder, the aver- age dose of which is 4 grains (0.26 Gm.), and the active principle cpi- nephrin, now generally accepted as the official name for proprietary prepara- tions, including adrenalin. A synthetic epinephrin has also been available, but there is no ground upon which it should be given preference over the active principle obtained from the adrenals. As shown by Shultz, Cushny, and others, all synthetic pro- ducts are about one-half the strength of the natural. The solution of epinephrin available is uniformly of 1 : 1000, the doses of which are: By the mouth, 10 to 30 minims (0.6 to 1.8 c.c.) ; intramus- cularly or hypodermically, if the region 746 ANIMAL EXTRACTS (SAJOUS). is massaged, 3 to 15 minims (0.18 to 0.9 c.c), always in free dilution with saline solution. Intravenously, it should only be given drop by drop in large dilution with saline solution, the latter being used as in hypodermoclysis. The use of strong solutions of 1 : 1000 solu- tion intravenously is always fraught with considerable danger. Rectally it may also be used freely diluted. Uterine injections are dangerous unless the solution be very weak. The vaginal portion of the uterus can 1)e rendered anemic effectually and safely by injection of only 10 c.c. (2^ drams) of 200 c.c. (65^ ounces) of salt solution containing merely 1 c.c. (16 minims) of the 1 per thousand solution of suprarenin — there is no need to use a stronger concentration. Neu (Zentralbl. f. Gynak., July 24, 1909). Two fatal cases due to the use of suprarenin injected into the cervix for operative purposes. The writer uses a very weak solution injected in considerable amount. It is not the amount of the drug or of the solu- tion used, but the concentration of the solution, that does harm. A large amount of a weak solution can be used without danger, while a small amount of a strong solution will be fatal. Braun (Zeit. f. Gyn., July 24, 1909). As I pointed out in 1907, it is very doubtful whether epinephrin, adren- alin, or any of the adrenal active prin- ciples are physiologically active in any but hypoadrenic or zveak individuals. This I attribute to the fact that gas- tric secretions give the oxidase reac- tions (guaiac, etc.), thus showing that they can oxidize them before they reach the circulation at all, and are thus deprived of their physiological properties. In hypoadrenic subjects, however, even the oxidized product (oxyhemoglobin) is taken up from the intestinal canal and assimilated. Adrenalin injected subcutaneously or into the peritoneum in laboratory animals has a marked toxic action and no adrenalin appears in the urine. On the other hand, 20 times this dosage and more, given by the mouth, causes no signs of toxic action, while considerable amounts of adrenalin are eliminated in the urine. The author thinks that under the in- fluence of the digestive juice and of the mucosa the adrenalin becomes bound in some way which deprives it of its physiological and toxic properties. Falta (Wiener klin. Woch., Dec. 23, 1909). This does not apply to the dried gland, probably because the active prin- ciple is bound up in organic combina- tion. S. Solis-Cohen found, more- over, that, by masticating the dried gland without swallowing it, the physiological effects manifested them- selves. If for some reason or other injections are impracticable the same dose of the 1 : 1000 solution on a lump of sugar, inserted between the cheek and gums, as practised by Rolleston, or adrenalin tablets, containing ^/^q gram (1 mg.), placed under the tongue, will serve the same purpose though somewhat more slowly. The active principle proper, is absorbed from the colon, especially when administered with saline solu- tion as previously stated. At the suggestion of Sollmann, the writer confirmed these effects by a series of experimental investigations. The effects were often found to ap- proach and sometimes to be parallel with those produced by rapid intra- venous injection, owing, doubtless, to the very great vascularity of the region. The injected material, in fact, was found at times'to pass di- rectly into the venous circulation, as shown experimentally. The adminis- tration of adrenalin in this manner clinically could possibly be of serious ANIMAL EXTRACTS (SAJOUS), 747 moment, such as causing a sudden rise of blood-pressure in cardiovas- cular disease, arteriosclerosis, etc. In conditions of circulatory collapse necessitating rapid stimulation, the injection of adrenalin into the sub- mucosa of the nasal septum, or tur- binals might be of much value. J. D. Pilcher (Jour. Amer. Med. Assoc, July 18, 1914). Epinephrin, i.e., adrenalin, is also conveniently put up as an inhal- ant, ointment, and suppositories, the strength being also 1 : 1000 in neutral oil, petrolatum, or oil of theobroma in the order of the preparations named, and some mild antiseptic to preserve the latter. Contraindications. — Fridericia (Ugeskrift f. Laeger, Dec. 9, 1915) enumerates the contraindications against subcutaneous in- jections of adrenalin. He found in litera- ture 5 deaths following injections. In 1 of these a large dose (0.6 Gm.— 10 grains) had been injected into a vein in a much debilitated patient with infarction of the lungs, granular nephritis and arterioscle- rosis. In all the others the epinephrin had been injected into the muscle of the uterine cervix while the patients were under the influence of chloroform. He has also found 2 deaths on record after subcutaneous injection of adrenalin, but these were in infants, only 3J/2 months old. A number of clinicians have reported un- favorable experiences with subcutaneous injections of adrenalin in cases of heart or valvular defects and nephritis with high blood-pressure. On the other hand, testi- mony is constantly accumulating as to the value of adrenalin in sudden heart weak- ness in the course of acute infectious dis- eases. It is harmful where signs of a val- vular defect or hypertrophy of the left heart exclude bronchial asthma. With cardiac asthma there is no expectoration or merely reddish foamy masses. Fine moist rales may be heard with cardiac asthma while with asthma of the bronchial type there are rhonchi. UNTOWARD EFFECTS.— In the frog toxic doses produce a temporary- paresis, the muscles acquiring marked rigidity. This is ascribed by some to poisoning of the spinal cord, by others to a direct action on the muscles. In mammals large doses given subcuta- neously cause excitement, tremor and vomiting, paralysis beginning at the posterior extremities, polyuria, and dyspnea, death ocurring either through respiratory failure or cardiac arrest. In the cat, however, which bears larger doses than other animals, the respira- tion ceases, as a rule, before the heart's action is arrested. This is due to pul- monary edema, according to some authors and to paralysis of the res- piratory centers, according to others. When the poison is injected into a vein the morbid effects are preceded by a very rapid and marked rise of the blood-pressure. Man is more susceptible to the action of adrenalin than animals. While a subcutaneous injection of 1 dram (4 c.c.) of a 1 : 1000 solution will hardly aft'ect a rabbit, one-third of that quan- tity has produced untoward effects in normal as well as in tuberculous sub- jects (Souques and Morel), e.g., ver- tigo, nausea, vomiting, severe pain un- der the sternum similar to that of angina pectoris, and a feeling of con- striction about the chest, a rapid pulse, dyspnea, cold sweats, and coldness of the extremities. In a case of pneumonia in a man of 65 years, injected subcutaneously 5 minims (0.3 c.c.) of 1:1000 solution adrenalin. About a minute after the drug was given, the patient became restless, dyspneic, facies blanched, eyes fi.xed, and complained of a con- striction sensation around the body on the level with the heart. His pulse became almost imperceptible and thready. The condition re- sembled an attack of angina pectoris. An injection of an oil solution of 3 748 ANIMAL EXTRACTS (SAJOUS). grains (0.2 Gm.) of camphor was im- mediately given, which acted with re- markable readiness in combating the attack. L. J. Friedman (Med. Sum- mary, Aug., 1915). [This is because he failed to dilute suffi- cient!}' the dose administered. C. E. DE M. S.] Intoxication may also follow the use of adrenalin when injected into cav- ities, such as the vagina, the rectum, the urethra, when the mucous mem- brane is abraded, lacerated, or denuded, thus rendering its absorption possible. The uterus and urethra appear to be especially sensitive. Case of a man aged 26 weighing 190 pounds, heart and lungs normal, in whom, to arrest bleeding caused by manipulation of the urethra to render a stricture passable, 10 minims of a 1:1000 solution of suprarenal principle were injected through an Ultzman instillator. The patient im- mediately complained of pain in the stomach, and a condition of profound shock supervened. He complained of air-hunger, vomited, and lapsed into syncope. As the pulse became slower and finally disappeared, and death seemed imminent, V^o grain of strych- nine and ^00 grain of nitroglycerin were given hypodermically. In ten minutes the radial pulse began to re- turn, and within an hour the patient left the office unassisted. Next day progressive dilatation of the stricture was practised without the aid of the adrenal preparation. Link (Central States Med. Monitor, Sept.. 1907). The prolonged use of adrenal prepa- rations may induce chronic adrenalism, manifested by marked cardiac disor- ders, especially of the myocardium; dyspnea after slight exertion, tachy- cardia, high blood-pressure, polyuria, icteric staining of the conjunctiva, and marked increase in weight. Case of a man who during one year and nine months applied daily to the conjunctiva, as a treatment for con- junctivitis, a solution of adrenalin chloride. Palpitations, with marked increase of the arterial tension, car- diac dyspnea on exertion, and poly- urea, were followed by a yellowish tinge of the conjunctiva such as that observed in jaundice. A curious feature of the case was that the pa- tient gained in weight rapidly. Cessa- tion of the instillations and regula- tion of the diet caused a gradual retrogression of these symptoms, but there remained some cardiac weak- ness. K. Feiler (Med. Klinik, May 17, 1908). The writers observed 10 and 20 days after an injection in dogs, the charac- teristic phenomena of anaphylaxis on injecting another dose of %.-, grain (0.(X)1 Gm.) of adrenalin and a weak dose of thionin, normally inactive. The usual primary rise of pressure and the secondary depression were observed. Gautrelet and Briault (Soc. de Biol., July 12, 1913). Local applications are sometimes fol- lowed by untoward effects in the tissues to which epinephrin solutions are ap- plied. Repeated applications, especially with the atomizer, of anytJiing but weak solutions (1 : 10,000) to the nasal cavities or pharynx may give rise to edema of the nasal mucosa, the uvula, tonsils, or pillars of the fauces. This is ascribed by most writers to "violent vasomotor constriction of the blood- vessels" and the resulting "venous stag- nation." In some instances they cause persistent sneezing and acute coryza accompanied at times by severe pain in the upper portion of the nasal cavities. Case of a man aged 39, of good habits and good health, except for his periodic attacks of hay fever, who was advised by a lay friend to use one of the well-known preparations of the suprarenal gland, and supplied himself with the remedy and an ato- mizer in the summer of 1905. He used it several times a day during his attack. ANIMAL EXTRACTS (SAJOUS). 749 When the hay fever subsided he noticed that there was a fullness in his nose that did not disappear, but, on the contrary, became more marked. He was treated by his physician for a time without relief, and then sought the aid of a rhinol- ogist. The condition refused to yield to any form of treatment, and, symp- toms of Eustachian congestion super- vening, it became necessary to re- move portions of both middle tur- binates. After a long course of treat- ment he went to his home improved, but bearing traces of the condition with him. Two other very similar cases witnessed. B. H. Potts (Jour. Amer. Med. Assoc, Oct. 13, 1906). Adrenalin, when applied to the gums on cotton-wool — whether to stop bleeding or, as has been recom- mended in the preparation of cavi- ties, to control the saliva exuding from the mucous glands at the neck of the teeth — should be used with great caution. The cotton-wool with the adrenalin solution should be thor- oughly squeezed to remove excess before applying. The writer had occasion to witness recently a distinct case of adrenalin poisoning in which it had been used to stop bleeding. Evidently in this case the adrenalin had been applied freely, and, on pressure being used to the pad of cotton-wool, a few drops of the excess adrenalin had been squeezed out. The symptoms were alarming, being not unlike an epilep- tic seizure, and the patient remained in a collapsed condition for some hours after. Anonymous (Chemist and Druggist; Prescriber, March, 1911). Some cases have been reported in which sloughing and gangrene of the mucosa occurred. Elderly subjects are prone to this complication, accord- ing to Neugebauer. Postoperative hemorrhages are not infrequently noticed after the use of adrenalin, owing to relaxation of the severed vessels. In the larynx, epinephrin solutions cause an uncomfortable dryness by interfering with the formation of lubricating mucous. This is especially distressing to singers. In the eye their use in scleritis and other dis- orders may be followed by severe iritis. Instillations of a 1 : 1000 solu- tion in the Eustachian tubes have given rise to violent pain in the mid- dle ear, which was renewed whenever the remedy was thus administered. The use of adrenalin solutions, in the form of a spray at least, is con- traindicated in infections, owing to the danger of facilitating the entrance of pathogenic germs into the sinuses. The role I attribute to the adrenal secretion in oxidation, metabolism, and nutrition is as applicable to the unto- ward phenomena as it was to the thera- peutic action of the drug. Following the course of events from start to fin- ish, we have at first the effects of ex- cessive metabolism in all tissues : in the cerebrospinal system, excitement; in the muscles, tremor; in the kidneys, polyuria ; in the myocardium, violent contractions (palpitations) ; in the muscular coats of the vascular system, a marked rise of the blood-pressure. The latter in turn aggravates the proc- ess by causing congestion and en- gorgement of the capillaries (which are not, like the arteries, provided with a muscular coat) of all organs, including the lungs, causing edema of these struc- tures and dyspnea. As the contraction of the arteries proceeds, the aorta has to bear the brunt of the centrifugal pressure, giving rise to marked sub- sternal pain. When it becomes such that the arterioles obstruct the circu- lation the lethal phenomena are initi- ated : the pulmonary circulation being impeded, oxygenation fails to occur. 750 ANIMAL EXTRACTS (SAJOUS). asphyxia follows, and, the myocardium receiving too little blood to sustain its contractile power, the heart, already hampered by the pulmonary congestion, ceases to beat. In chronic adrcnalism the same in- terpretation obtains, the cardiac phe- nomena being ascribable mainly to the extra work imposed upon the heart by the resistance of the general vascular tension. The gain in weight is a nor- mal result of increased metabolic ac- tivity, i.e., overnutrition. After local applications the morbid effects are all the result of the action of the adrenal principle upon the vessels. The dryness produced by solutions sprayed into the larynx is due to defi- ciency of blood supplied to the acini and the resulting inhibition of their function. If this is kept up by repeated applications, the tissues, no longer nourished, may slough off, as has been noticed in the upper respiratory tract of aged subjects. The edema observed in this location is not active, as it is in the lungs, but passive, i.e., due to ex- aggerated relaxation of the vessels af- ter the intense constriction to which the drug had subjected them. This applies equally well to postoperative hemorrhage, and to the severe pain (due to passive congestion) in the middle ear after instillations in the Eustachian orifice. THERAPEUTICS.— Addison's Disease. — Textbooks of practice and therapeutics now teach pretty gen- erally that adrenal preparations are of value in Addison's disease. A personal study of the literature of the subject showed that out of 120 cases treated by adrenal preparations 25 had been suffi- ciently benefited to be restored to health — as far, at least, as the loss of adrenal tissue incurred through the local morbid process would permit. The one great factor in the treatment of this affection by means of adrenal extractives is to drop their empirical use, and it is only (and this applies to the use of any disease) when the im- portance of this fact will have been thoroughly grasped that the proportion of recoveries will be materially in- creased. Empiricism here may entail death. [E. W. Adams (Practitioner, Oct., 1903) refers to a group of 7 cases found by him in literature "in which alarming or fatal re- sults were presumably or possibly due to the treatment." He mentions, for instance, 2 cases reported by a prominent clinician treated with "suprarenal gland extract." The chart notes of the cases include the la- conic words : "Alarming collapse. One of the cases began to improve markedly when the extract was stopped." In the original paper reference is made to another case treated by suprarenal extract in which "similar collapse was noted." The dose was not mentioned. Such cases are apt to be regarded as examples of the sudden death sometimes observed in Addison's disease, to which Addison himself, Dieulafoy, Ander- son, Bradbury, and others have called atten- tion ; but this explanation does not hold. Guiol (Bull, de la Soc. medico-chir. du Var., Dec, 1906), having observed similar signs of intoxication and collapse, tried the "remedy'" in a normal subject and obtained the same morbid phenomena. Here, again, we are dealing with fatalities which occurred when the physiological functions of the organs, and, therefore, their mode of action as a therapeutic agent, were but slightly known. C. E. DE M. S.] The salient guides in the use of these preparations are the loiv temperature, which denotes deficient oxidation and metabolism, and the weak pulse, which points to a low vascular tension and inadequate cardiac dynamism. Im- provement of a given case is indicated by a gradual resumption of normal ANIMAL EXTRACTS (SAJOUS). /:) ;i conditions in these two directions, and by the return of bodily vigor, with more or less fading of the pigmenta- tion. As a rule, the more these various morbid phenomena are marked, the larger will be the initial dose required. In other words, marked hypothermia, a very feeble pulse, advanced bronzing, and great debility will indicate that a mere vestige of both adrenals is still active; the dose indicated, then, is that which will supply enough additional principle to raise the temperature and the blood-pressure to nonnal, but not beyond. A study of the 120 above- mentioned cases has shown that 3 grains (0.2 Gm.) of the desiccated gland three times daily was the most satisfactory dose to start with. If this fails to raise the temperature and the pulse tension or improve the case, the dose should be increased by 1 grain per day until it does, the case being watched closely. As soon as the nor- mal temperature is reached, the dose should no longer be increased, unless a tendency to recurrence of the hypo- thermia (gradually as the adrenals are being destroyed by the local morbid process) should render it necessary. In less advanced cases the initial doses should be correspondingly small, 2 or even 1 grain of the extract being ad- ministered three times daily, the dose decreasing in proportion as the disease is less advanced. Can we expect a cure from adrenal preparations? In most cases of Addi- son's disease the local process is tuber- cular— often limited to the adrenals. A number of examples suggest, however, that the tubercular process itself was benefited, and even cured, by the use of adrenal extract. It is always well, however, to treat simultaneously the tuberculosis on general lines. The writer observed a case due to adrenal tuberculosis which showed that marked increase in vitality and strength may be secured by supra- renal extract without as great an in- crease in the blood-pressure as would be expected. Judson Daland (Endo- crinology, July-Sept., 1918). A number of cases are on record in which, after apparent recovery, the cases died suddenly soon after ceasing the use of adrenal preparations. It is evident that even the possibility of curing the morbid process in the adre- nals does not replace the destroyed adrenal tissue. It is here that grafting would be of curative value, but only provided small fragments of adrenal tissue be inserted, and gradually in- creased in number until the tempera- ture and pulse indicate that compensa- tion for the functionless areas in the adrenals has been increased The 120 cases analyzed showed also, and my own experience has further demonstrated, that what is generally known as "adrenal extract," but which, in reality, is the desiccated adrenal gland (the glandulcc suprarcnales sicca of the U. S. P.), is by far the most sat- isfactory agent to use. Injections of adrenal fluidextracts are exceedingly painful — a fact which compromises the issue by introducing the element of shock — while the active principle, epi- nephrin, adrenalin, etc., sometimes- fails altogether to act. See, also .Addison's Disease, Treat- ment OF, this volume. Shock, Collapse, and Surgical Dis- eases.— This is another condition in which adrenal preparations show prominently their influence on metabo- lism. The function I ascribe to the adrenal secretion (to take up the oxy- gen of the air, and be carried to the tissues where its active principle aug- /52 ANIMAL EXTRACTS (SAJOUS). ments greatly the activity of this gas) involves the conclusion that it is a prominent factor in the sustenance of the body heat, a fact demonstrated by Reichert, Lepine, Morel, and others. Now, Kinnaman, in a comprehensive study of the temperature relationship to shock, concluded that as shock in- creased in severity the most uniform progressive factor was the fall in tem- perature. He states that "in one series [of cases] the fall in temperature was the sole cause of shock." The results of Crile with adrenalin in salt solution given very slowly and gradually for a considerable time thus find a normal explanation in my interpretation of the role of the adrenal secretion. He sup- plied the organism precisely with the substance which sustains the vital proc- ess in the tissue-cells. Indeed, he re- suscitated animals in this manner — with simultaneous artificial respiration — fif- teen minutes after all signs of life had ceased, and was able to keep a decap- itated dog alive over ten hours by this same procedure. That it was because the adrenal secretion is able to sustain tissue metabolism, i.e., the vital process itself, that such results were obtained seems self-evident. In the great war, most of the wounded arrived in a more or less pronounced state of shock and needed some restorative before being oper- ated upon. The writer has used ad- renalin in saline solution with good results. A half milligram (M20 grain) of adrenalin is mixed with 500 Gm. (1 pint) of saline solution and every patient in shock is injected with 500 Gm. (1 pint) of this mixture. Imme- diately after operation a second in- jection is made and 2 injections per day are given for several days; gen- erally, however, it is not needed after 2 or 3 days. The effects are marked increase in blood-pressure and a more ample pulse as well as improve- ment in the general condition. Du- pont (Arch, de med. et pharm. mil., Ixiv, 542, 1915). The rate of output of adrenalin in dogs and cats, after the blood-pres- sure had been permanently lowered by exposure and manipulation of the intestines, by partial occlusion of the inferior vena cava, by hemorrhage and by "peptone" injection, was found by the writers to be the same as before the lowering of the blood- pressure, within the limits of error of the methods used for assaying the epinephrin. A marked increase in the rate of output of adrenalin was pro- duced by strychnine. Stewart and Rogofif (Amer. Jour. Physiol., Feb. 1, 1919). This applies not only to shock, but also to surgical heart-failure, collapse from hemorrhage, asphyxia, and sub- mersion. The adrenal principle (su- prarenalin, adrenalin, etc.) promotes energetically, as a catalyzer and con- stituent of the hemoglobin, the intake of oxygen and its utilization by the tis- sue-cells, including the muscular ele- ments of the cardiovascular system, and thus causes them to resume their vital activity. It should be very slowly administered intravenously, 5 minims of the 1000 solution to the pint of warm (105° F.) saline solution. In urgent cases 10 drops of suprarenalin or adrenalin in 1 dram of saline solu- tion can be used instead, and repeated at intervals until the heart responds. Artificial respiration hastens its effects. In collapse from weakness of the vasomotor center, such as is liable in pneumonia, diphtheria, and perito- nitis, good results may be obtained with a suprarenal preparation in- jected into a vein, or, diluted with salt solution, injected subcutaneously. Case of uncomplicated ileus in which by this means it proved possible to tide the apparently moribund patient past the danger stage after two days ANIMAL EXTRACTS (SAJOUS). 753 of fecal vomiting, and thus permitted a successful operation. Heidenhain (Deut. Zeit. f. Chir., April, 1910). Research showing that epinephrin has no cumulative action. Its action only on direct contact. The contin- ual infusion of a weak solution of epinephrin may prove a useful meas- ure in therapeutics. It is thus pos- sible to send the solution continu- ously into a vein and thus keep up the blood-pressure permanently while this is being done — the effect being dependent on the concentration of the solution, not on the absolute amount of epinephrin infused. Straub (Miinch. med. Woch., June 27, 1911). During the war the writer in 1 year encountered 15 cases of what seemed to be Addison's disease, in men in active service, except that it displayed a tendency to spontaneous subsid- ence, even in apparently the gravest cases. A few weeks of rest and quiet, abstention from meat, and treatment with suprarenal extract soon banished all the symptoms. In two of the cases there was what Loeper has described as suprarenal dyspepsia, notably improved by epinephrin. The symptoms developed in all after a period of exhausting fatigue, an in- fectious disease, or gassing.. The asthenia was the most striking symp- tom, more mental than physical. For months the men were incapable of reading a paper, writing a letter or even answering questions that re- quired any thought. Improvement in this respect was rapid under epi- nephrin treatment. The blood-pres- sure was low. but this is common among all the men at the front. A certain tendency to bronzing of the skin was perceptible in all the 15 cases. The suprarenals, after the patient's recovery are left below par, and re- sumption of active service is ex- tremely likely to rearouse the old trouble, and the next time it might prove grave beyond recuperation. Carles (Jour de Med. de Bordeaux, July, 1918). Reference was made under "Un- toward Effects" to the dangers at- tending the use of the adrenal prin- ciples in surgery to produce ischemia at the seat of operation. Though such effects are not often met with, the fact remains that they should be borne in mind and the principle that it is the free dilution of epinephrin, adrenalin, etc., that protnotes safety. Surgical operations can also be per- formed without loss of blood, except from the larger vessels, in almost any organ by injecting locally 8 to 10 minims of a 1 : 1000 solution in four or five times the same quantity of saline solution. Care should be taken not to inject too large a dose lest the untoward effects described earlier in this article occur. Solutions of 1 :10,- 000 or even 1 : 100,000 are quite suffi- cient sometimes to produce a blood- less field by causing local constriction of the blood-vessels. Toxemias and Bacterial Infections. — This is a recent and important de- velopment of organotherapy. Abel- ous and Langlois, Charrin, Oppen- heim, and others have laid stress on the antitoxic functions. The process through which this protective role was carried out by these organs be- ing admittedly unknown, I submitted in 1903 and 1907 ("Internal Secre- tions") evidence tending to show that the adrenals and thyroid were the sources of two substances as promi- nent agents in the immunizing pro- cess— the thyroid carr^'ing out, we have seen, the role of opsonin (con- firmed by Fassin, Stepanoff, and Alarbe), while the adrenal secretion acted as amlioceptor. While I do not regard these two agents as the sole participants in the immunizing 1— iS 754 ANIMAL EXTRACTS (SAJOUS). process, the fact remains that the ad- dition of either of them to the blood enhances to a certain extent its func- tional activity. Especially is this the case in view of the fact that adrenal secretion, as previously stated, serves to sustain oxidation and tissue me- tabolism. By doing- so it activates the functions of all tissues, including- those concerned with the production of protective substances. The blood thus finds itself richer in these sub- stances and more active as a germi- cidal and antitoxic agent. Infectious diseases constitute the principal field in which the adrenalin treatment is of service, and the writer has employed adrenalin successfully in many cases of severe collapse in connection with scarlet fever, pneu- monia, and typhoid fever. He does not hesitate to use larj^e doses. He invariably administers it by subcu- taneous injection and has observed no after-effects. Kirchheim (Miinch. nied. Woch., Dec. 20. 1910). Adrenalin, injected intravenously, in saline solution, is indicated in the treatment of peritonitis, used con- tinuously. The action of adrenalin on the diseased organism must be borne in mind. By using the drug in very dilute solution weakened systole becomes strengthened and in time becomes normal in force. The weak- ened heart and lowered blood-pres- sure of peritonitis, also due to a toxic substance, indicate the same measure. Holzbach (Miinch. med. Woch., May 23, 1911). One c.c. (16 minims) of adrenalin injected subcutaneously in acute in- fections, typhoid, pneumonia, etc., was found by the writer to cause a sudden rise of pressure with but a slight increase of the amplitude of the pulse; 0.75 c.c. (12 minims) pro- duced less rise in pressure but greater pulse amplitude both on account of increased systolic and lowered dias- tolic pressure; 0.5 c.c. (8 minims) did not apparently cause any constriction of the peripheral blood-vessels, but by dilating the venous system and acting on the nerve mechanism of the heart, it improved the venous circulation and consequently the nutrition of the heart. The large doses may be used promptly in postoperative shock, collapse, or acute poisoning; otherwise the smal- ler doses are safer and productive of better results. S. M. Mansvetova (Roussky Vratch, June 21, 1914). Epinephrin or adrenalin may be used advantageously in infectious diseases, but to avoid untoward ef- fects it is best given well diluted — 10 to 15 drops of the 1 : 1000 solution in not less than 1 dram of water, admin- istered very slowly. If g-iven intrav- enously it is preferable to administer the saline solution as usual, and then to introduce the needle of the hypo- dermic syringe into the rubber pipe, injecting- a drop of the adrenal active principle (preferably supracapsulin 1 : ICKX)) into the stream of saline solution at short intervals. In this manner much more adrenal principle can be introduced with a minimum of danger. The writers relate the following cases: Man, aged 44, had recently gone through an attack of quinsy, after which he suffered from what was regarded as lumbago. The next symptoms were those of probable malignant disease of the left side of the neck — a parent lesion and en- larged regional hmphnodes. He also began to emaciate without apparent cause, which reinforced the diagnosis of malignancy. It was thought that the tumor in the neck was a second- ar}' nodule, but no primary growth could be detected anywhere. The re- mainder of the finds of a systematic examination were also negative with the exception of vascular hypotension. Thi." first drew attention to the ad- renals and Sergent's white line was repeatedly obtained. Poultices ap- ANIMAL EXTRACTS (SAJOUS). 755 plied to the loins brought out a brown pigmentation. An injection of adrenalin increased the blood-pres- sure without causing glycosuria. The lumbalgia had persisted. The pa- tient was interned technicalli' for a slight bronchitis, but in the hospital he rapidly sank and died of adynamia. Autopsy revealed a complication of affections, the primary growth being an ulcer of the base of the tongue with numerous metastases, including the visible ones of the neck. The right adrenal was the seat of a can- cerous metastasis, while its fellow ap- peared to be hypertrophied. The second patient was a man of 24 years, who went through a typhoid fever complicated with perforation and peritonitis. Owing to the profound state of depression, a surgical opera- tion was out of the question. The presence of the white line and low blood-pressure showed the condition of the adrenal functions. Death was preceded by the development of acute hemorrhagic diathesis. There was a marked anatomical foundation for the adrenal insufficiency, but the lesions could not be interpreted beyond evi- dences of degeneration of some sort. Such lesions have frequently been encountered in death from acute in- fectious diseases, but the rationale is not apparent, although the adrenals have evidently lost most of their lipoid content. Betchov and Demole (Revue med. de la Suisse Romande, June, 1918). The recognition of the antitoxic property of the adrenal active principle has recently caused it to be employed as an antidote in strychnine poison- ing, a fact pointed out by Abelous and Langlois in 1898. These authors also found it to oppose the toxicity of nicotine, while Oppenheim ob- tained similar results with phos- phorus. Exner has shown that intraperitoneal injections of adrenalin diminish the rate of absorption of strychnine intro- duced into the stomach, and the writer, therefore, decided to try whether adren- alin given by the mouth would exert a similar effect. He first found that adrenalin could exert its vasocon- strictor action after the arteriolar wall has been subjected to the action of cyanide of potassixun, and then studied its effects upon rabbits poisoned by the cyanide. He was able) to bring about recovery after longer periods than in rabbits which had not received adren- alin. He recommended the following procedure for cases of cyanide poison- ing in man. Adrenalin should be given immediately, 9 c.c. (i.e., 3 drams) of the 1 : 1000 solution diluted to 90 c.c. saline solution ; then Martin and O'Brien's antidote if available. This consists of 30 c.c. (1 ounce) of a 23 per cent, solu- tion of ferrous sulphate, 30 c.c. of 5 per cent, solution of caustic potash, and 2 Gm. (30 grains) of magnesia. The first two solutions should be kept in hermetically sealed phials. The three substances should be mixed when re- . quired and immediately taken. The principle of the method is the forma- tion of Prussian blue, which is prac- tically innocuous. The stomach should then be washed out and a further dose of about 5 c.c. (IK' drams) of 1:1000 adrenalin solution diluted to 50 c.c. should be given. A brisk saline purge is also recommended, to be administered soon afterward. J. L. Jona (Intercol. Med. Jour, of Austral., July 20, 1909). Adrenalin found experimentally to counteract the toxic symptoms induced by strychnine in the frog. Similarly, if adrenalin and str\'chnine are in- jected, guinea-pigs will tolerate sev- eral times the fatal dose of the latter drug. The action of adrenalin is actually antagonistic and not de- pendent on vascular contraction, with slower absorption, as some authors claim, since other poisons are not affected in their toxicity. The an- tagonism is very similar to that between atropine and muscarine. Falta and Svcovic (Berl. klin. Woch., Oct. 25, 1909; Merck's Archives, Jan., 1910). 756 ANIMAL EXTRACTS (SAJOUS). Postoperative Intestinal Atony. — are dealinig, therefore, not with a local To the adrenals seem also to belong product, but with a component of all the credit of offering the opportunity tissues (being as such what Starling to antagonize this disorder. When in has termed a "mamma hormone"), 1903 I submitted the opinion that the and which when present in unusual thyroid secretion enhanced the activ- quantities in any organ is capable of ity of the adrenals — a view since sus- enhancing correspondingly its func- tained by several experimenters — and tional activity owing to its influence that the adrenal secretion on the on local oxidation and metabolism, other hand, influenced the functional Another hormone has been ob- activity of the pancreas, pituitary tained from the gastric mucosa by body, and other organs, the state- Dohon, Alarxer, and Zuelzer (Berl. ment created some surprise. This klin. Woch., Nu. 46, 1908), which was feeling died out, however, when, three found to enhance intestinal peristal- years later, Starling termed hormones sis. But inasmuch as it is (from my a group of substances secreted by viewpoint) a ubiquitous component various organs which could enhance of all tissues, and the difficulty of the functions of other organs. Pre- collecting it during digestion being cisely as I had previously held, these obvious, search for it elsewhere sug- hormones were secreted, according gested itself. It was found in ample to Starling, by the organs which pro- quantities in the spleen— that junk- duced them in the course of their nor- shop in which red corpuscles (which, mal functions, and reached the distant as I suggested in 1903, are the com- structures they influenced through mon carriers of the adrenal principle) the intermediary of the blood. What are broken up along with other cells. I termed the adrenal system owed That the splenic hormone referred to in great part its functional activity 's not purely the adrenalin-laden al- to this chemical co-ordination: the buminous constituent of the hemo- adrenal secretion being especially globin derived from red corpuscles prominent in the process owing to '» self-evident, since leucocytes with the function 1 attributed to it, viz., their nucleoproteid granulations, to sustain oxidation and metabolism ^^'^'' tr>^psin-like cytase, and other as a constituent of the hemoglobin ferments are also broken up in the molernle spleen. The fact remains, however, T^ ,. J o 1- 1 ■ that this splenic hormone specifically Bayliss and Starlmg termed secretin . , . . , • , • , . .... . , stimulates mtestmal peristalsis to a a hormone formed in the intestinal , , , , • . n . , degree so remarkable experimentally mucous membrane under the influence ^i ^ „ , j-, • .,, that it mav be readilv seen in the ex- of the hydrochloric acid from the p^^^^ j^^^'^^j^^ ^^ experimental ani- stomach, which is the chemical ex- ^^j^ ^^^ ^^ ^^^^^^ minutes after an citant of the pancreatic secretion, intravenous injection. Now, from my viewpoint, this is not The applications of this peristaltic a specific excitant; I showed in 1907 hormonei in surgery are mainly in (vol. ii, "Internal Secretions," p. those conditions of intestinal paresis 861) that it presented several of the following operations on the intestine, properties of adrenal extractives. We and particularly where purgatives, ANIMAL EXTRACTS (SAJOUS). 757 castor oil included, bring on no re- sults. It is also indicated in all forms of stubborn constipation due to intes- tinal atony. Miscellaneous Disorders. — The foregoing disorders may be said to rep- resent those in which adrenal prepara- tions are more effective than any other preparation at our disposal. There are several others, however, in which they will probably prove of considerable value, when sufficient trial of them in practice will have warranted a final pronouncement. These are : — Hemorrhage from the pharyngeal, esophageal, gastric, or intestinal mucous membrane. Here the mastication of adrenal substance or the use of pow- dered adrenal substance in 5-grain capsules arrests the flow, by causing active metabolism in the muscular ele- ments of the arterioles of the mucosa and constriction of these vessels. The active principle, epinephrin, supracap- sulin, etc., has also been given by the mouth in 10- to 15- drop doses. To avoid hemorrhage during the re- moval of placental rests after abortion the writer exposes the cervix and prac- tises deep injection of the following solution into several points of the cer- vical tissue, — either 1 c.c. of 1 per cent. or 2 c.c. of Yi per cent, cocaine solu- tion to which 3 drops of 1 : 1000 adren- alin solution has been added. After waiting ten minutes, the operation of emptying the uterus is practically blood- less and the organ is firmly contracted, though patency of the cervix remains. O. Crasser (Zentralbl. f. Cynak., June 19, 1909). The writer has seen within the past year 5 cases of vicarious hemorrhage, 1 of the rectum, from the inner can- thus of the nose, etc., in which he pre- scribed the suprarenal extract — adren- alin 1 : 1000, giving IS drops every three hours until it ceased — and secured prompt relief. J. W. Trwin (Med. Brief, Aug., 1911). Spontaneous recurrent epistaxis is usually due to ulceration over capil- laries or a vessel in the anterior nares. but at times it is difficult to locate the precise area from which the hemorrhage comes. This may be overcome by an application of ad- renalin solution to the anterior por- tion of the septum. This blanches the whole mucosa except at the spots which give rise to the bleeding. These then stand out clearly against the pale surface as red, circular areas. W. Lapat (Jour. Amer. Med. Assoc. Ixvii, 1159, 1916). Asthenic cardiac disorders with dila- tation of the right ventricle, dyspnea, and possibly cyanosis and edema, own- ing to the direct action of the adrenal principle on the right ventricle and improved oxidation and metabolism in the cardiovascular muscles and the tissues at large. Tablets of from % to 1 grain of the desiccated gland can be taken after meals. Adrenalin caused in the terrapin a disappearance or a diminution in the tonus waves observed in the sino- auricular muscle preparation, and a simultaneous increase in the force and amplitude of the contraction, and in some instances an increase in the rate of contraction. When the solu- tion was strong, the waves ceased al- most immediately; when a more di- lute solution was used, onlj^ a few tonus waves appeared after the addi- tion of the adrenalin to the Ringer's solution. The length of time re- quired after an injection of adrenalin, before the recurrence of the waves, varied directly with the strength of the adrenalin solution used. Oxygen added to Ringer's fluid seemed to hasten the process of recovery, which might be only a matter of hastening the oxidation of the adrenalin. Gru- ber and Markel (Jour, of Pharm. and Exper. Therap., Aug., 1918). The writer tested the effect of the injection of 0.5 c.c. (8 minims) of a 1:1000 solution of adrenalin in nor- mal soldiers and in soldiers suffering 75S ANIMAL EXTRACTS (SAJOUS). from "irritable heart." In only 1 of the 27 control cases was there a sug- gestion of hypersusceptibility to epi- nephrin. In 65 patients the epi- nephrin test was positive in 39, doubt- ful in 6 and negative in 19. The most important symptoms of the re- action were the presence of tremors, sweating, flushing, pulsation of peri- pheral blood-vessels, general nervous- ness and increase in blood-pressure, pulse-rate and depth of respiration. Furthermore, the "irritable heart" cases showed an increase in basal metabolism and in blood sugar more marked than in normal individuals. The electrocardiogram showed most constantly a slight decrease of the height of the T-wave., In individual cases other abnormalities were seen, such as increase of sinus arrhythmia, prolongation of P-R interval, partial heart block, inversion of the T-wave and the production of ventricular ex- trasystoles. The writer advises the use of epinephrin as an aid in the diagnosis of "irritable heart." Pea- body (Jour. Amer. Med. Assoc, Ixxi, 1912. 1918). Asthma. — To arrest the paroxysms, by augmenting the jnthnonary and tis- sue intake of oxygen and the cardio- vascular propulsion of arterial blood. From 5 to 10 minims of the 1 : 1000 solution of adrenalin in 1 syringeful of saline solution should be injected hypo- dermically, very slowly, massaging the part so as to insure absorption of the solution. [The effect is so rapidly obtained and satisfactory that the patient is sometimes entrusted with a syringe and allowed to treat himself. But this is a dangerous procedure. 1 have observed, in consultation, a death which could undoubtedly be attrib- uted to this cause. C. E. de M. S.] Case in which alarming manifesta- tions were produced by the hypoder- mic administration of adrenalin. The man l)ecame cyanotic and had the most severe rigors the writer had ever seen; but the asthmatic attack was immediately relieved. After sub- sidence of the rigor the only ill effect was muscular soreness for 24 hours. S. J. Meyers (Miss. Valley Med. Jour., Nov., 1917). Effusions. — To prevent the recur- rence of serous effusions in the pleura, the peritoneum, the tunica vaginalis, etc., after aspiration, by reducing the permeability of the local capillaries and restoring the circulatory equilibrium. From 8 minims to 2 drams (according to the size of the cavity) of supraren- alin or adrenalin, in four times the quantity of saline solution, should be injected into the cavity. Disorders of Pregnancy and Par- turition.— The most useful employ- ment of adrenal preparations in dis- orders of this class is in obstinate vomiting of pregnancy. This was suggested by the frequency and ob- stinacy of vomiting in Addison's dis- ease and the beneficial influence of adrenal gland over this symptom. The benefit is probably due to the more active destruction of toxic wastes — which are increased during preg- nancy owing to the presence of the fetus — a function in which we have seen the adrenals take part. Severe case of hyperemesis gravi- darum of more than two months' duration treated with marked success by means of adrenalin in small doses. Various remedies had been tried, and artificially induced labor was seriously contemplated. S. Rebaudi (Gazz. degli Osped.; Zentralbl. f. Gynak., Nu. 44, 1909). Cancer. — The fact that the cancer- ous growths in mice and rats had been caused to disappear by the injec- tion of the active principle into these growths suggested that the latter might also prove efficacious in man. About all that can be said for the present is that the results warrant further trial. ANIMAL EXTRACTS (SAJOUS). 759 Second series of experiments in the Konig Charite on private patients on a larger scale, based on Reicher's experiments in animals. The writer gave to men an average of 0.2 to 0.3 Gm. to begin with and increased up to 1 Gm. of the original solutions of ad- renalin, selecting cases which did not suffer from bad heart disease or cal- cification of arteries. The best results were obtained in a boy of 12 years who suffered from sarcoma of the vertex. Within three and a half weeks the tumor was reduced to one-third of its size. The remaining third was made to disappear under the Christian Miiller method of X-rays and high frequency combined. Since six months the tumor has undergone complete retrogression ; no recurrence has occurred. The writer also reduced temporarily sev- eral cases of malignant lymphoma. He has since tried to treat other in- operable tumors, among others a mel- anosarcoma, which was identified as such under the microscope. It was a metascasis in the groin which occurred one and a half years after excision of the primary tumor on the dorsum of the foot. Within one and a half months it had increased to the size of of a man's fist. In three months he was able to reduce its size very little, but, at least, it has become stationary, while before it was growing very rapidly. It is remarkable that during the treatments the patients increased much in weight — up to 14 pounds in his series. There must be a constant anomaly of metabolism somewhere. Reicher (Berl. klin. Woch., Nu. 20, 1911). The desensitizing of the skin by means of adrenalin permits the use of nearly double the dose of the X-rays for a period of from fourteen to eighteen days. The most important indication for this method is the treatment of malignant tumors sit- uated subcutaneously. Reicher and Lenz (Miinch. med. Woch., June 13, 1911). Case of squamous-celled carcinoma of the cheek treated with X-rays and later with radium, with very little, if any, improvement. To assist the penetration of the rays, applications and injections of adrenalin (1:1000) were employed. The injections were discontinued, being followed by local edema, but the applications were continued for some time. Great im- provement resulting, a daily dress- ing of lint soaked in adrenalin solu- tion was applied, the radium treat- ment being discontinued. The ulcer healed gradually and 6 years later there had been no recurrence. L. C. Peel Ritchie (Lancet, June 29, 1912). The writer saw benefit follow a single injection of adrenalin in can- cer, evidently made as a test. Rosen- berg was obliged to discontinue ad- renalin injections because of the pain caused. Graffner (Berl. klin. Woch., Nov. 20, 1912). Case of carcinoma of the tongue, the size of a hen's egg, which had necessitated tracheotomy, in which the writer tried injecting a few drops of adrenalin, graduallj^ increasing to 2 Gm. (30 grains) a day. The tumor began to undergo gangrene and to be thrown off, the remaining mass being snared off. Holscher (Annales des Mai. de I'Oreille, du Lar., du Xez et du Phar., 7 Liv., 1912). Case of inoperable carcinoma of the pharynx with cachexia and swell- ing of the cervical glands treated with a tabloid containing fresh thy- roid 6 grains (0.4 Gm.), adrenal ^ grain (0.048 Gm.), pituitary i/ic grain (0.004 Gm.) one night and morning,. The improvement was slow but steady. In 4 months, an additional capsule being given daily, she could swallow all foods if well masticated, except meat. In 5 months she re- sumed work, improving steadily, hav- ing considerably increased in weight. J. T. Shirlaw (Liverpool Med.-Chir. Jour., July, 1913). Osteomalacia. — In osteomalacia the adrenal preparations find a normal in- dication in view of their stimulating in- fluence on metabolism and, therefore, general nutrition, in which the osseous system must normally partake. This 760 ANIMAL EXTRACTS (SAJOUS). beneficial process is further enhanced by the fact that the thyroid apparatus is itself stimulated through the same cause, and that the thyroid secretion, as shown by Macallum, Parhon, and others, actively promotes calcium me- tabolism. The writer collected 47 cases treated with adrenalin, 11 pregnant and 35 non-pregnant women. Of the former 45 per cent, were cured and about 18 per cent, improved; of the latter 17 per cent, were cured and 40 per cent, improved. R. Cristofoletti (Gynak. Rundschau, v, 113; 169. 1911). LOCAL USE.— To check hemor- rhage from wounds, adrenalin can be used in various organs. In free hemorrhages from mucosre or in simple congestion of the latter, local application of the extract is quite sufficient for hemostasis. In a parenchymatous hemorrhage, in the course of an operation, the indication is filled in the same manner. Satre (Le Prog. Med., July 8, 1917). Bates, Dor, and many other oph- thalmologists have introduced the lo- cal application of a weak solution to the conjunctiva to produce a blood- less field, and also to enliance the local effects of cocaine, atropine, es- erine, and other agents used in the eye. Weak solutions may also be used in conjunctivitis. Instillations of 4 to 5 drops of the 1 : 1000 solution of adrenalin or sub- conjunctival injections of a smaller quantity causes a primary reduction, followed by a marked increase in ten- sion. Subsequently there is a secondary reduction of tension. These changes are observed in normal as well as glaucomatous ej^es. The reaction in normal eyes is not very great, but in glaucomatous eyes it is quite marked. In normal eyes, the effect of the adren- alin passes away in a few hours, whereas in glaucomatous eyes the effect continues for several days. In a certain number of cases of glaucoma the adrenalin produced a lowering of tension, whereas in others it caused attacks of acute exacerbation. Repeated instillations in normal eyes are apparently without much effect, but in glaucomatous eyes there is a marked increase in tension after the final in- stillation. The result of the combined use of eserine and adrenalin on tension indicate the two opposing forces are at work. Therefore, in eyes that have a predisposition to glaucoma it is advis- able to combine eserine with the adren- alin. J. Rubert (Zeit. f. Augenheilk., Bd. xxi, S. 97, 224, 1909). In 50 cases of conjunctival hyper- emia from causes varying in nature from simple congestion due to eye- strain to the most severe types of conjunctivitis, a single drop of ad- renalin chloride solution, 1:5000, in the conjunctival sac almost imme- diately caused a blanching of the membrane, commencing in about ten seconds, and reaching a maximum in from five to ten minutes, the effect lasting from one-half to two hours, according to the nature of the case. The blanching effect may be obtained by even a solution of from 1 : 12,000 to 1 : 10,000 in from thirty seconds to two minutes. A solution of 1 : 2000 was found to give the best results in operative work upon the eye, causing no irritation that could be noted upon close observation. A 2 per cent, solu- tion of cocaine hydrochloride was used ten minutes prior to the instillation of the adrenalin, when operation was con- templated, in order that the effect of the anesthetic might not be interfered with, thus insuring a painless and almost bloodless result. MacFarlane (Can. Practitioner, June, 1909). This applies as well to the local use of adrenal extractives in the nose, pharynx, and larynx, a weak solution of cocaine, 4 per cent., for example, acquiring the power of 15 to 20 per cent, solution, both as anesthetic and styptic. Combined with B-eucaine (5 c.c. of 1 per cent, solution), supra- ANIMAL EXTRACTS (SAJOUS). 761 renalin, or adrenalin, 3 drops of the 1 : 1000 suffice when injected in small quantities into the tissues, or. applied locally to mucous membranes, are quite effective for operations in al- most any reg"ion, including the urethra. The cocaine and adrenalin solution referred to above is equally effective, the operation being performed after three or four minutes. These so- lutions are extensively used, especially for dental, uterine, rectal, and urethral operations. Hemorrhoids. — Bouchard intro- duced the use of tampons soaked in adrenal preparations for the treatment of this condition. In external piles, es- pecially if there is great distention and hemorrhage, 20 drops of suprarenalin in 2 drams of saline solution applied with a compress relieve greatly the conges- tion and the pain. A small quantity of cocaine enhances these beneficial ef- fects. The writer obtained a rapid retrac- tion of hemorrhoidal tumors b\' giv- ing a single injection of 0.5 c.c. (8 minims). This dose will reduce a hemorrhoid the size of a walnut within a week's time. A hemorrhoid the size of an apple was greatly re- duced by 15 injections given during 7 weeks. The drug is injected under the mucosa, as is done for anesthesia of the mucous membrane. H. Kruk- enberg (Miinch. med. Woch., July 30. 1918V Neuralgia, Sciatica, and Neuritis. — To subdue and sometimes arrest pain in these disorders, by causing ischemia of the hyperemic and, therefore, over- sensitive nerves. One to 2 minims of a 1 : 1000 suprarenalin or adrenaHn ointment applied by inunction over the painful area. Cutaneous Disorders. — Local appli- cations of the 1 : 1000 solutions of su- pracapsulin, adrenalin, etc., may be used advantageously to assuage pain and counteract inflammation, which they do by causing constriction of the arterioles. Among the conditions in which they have proven useful are toxic erythema, urticaria, acne, sun- burn, bee-sting, eczema, chilblains, ar- thralgia, arthritis, varicose veins, bums. X-ray dermatitis, and herpes zoster. The vasoconstrictor property of epinephrin was taken advantage of by the author in 3 cases of erythema of the face ("red nose"), 2 of the pa- tients being young men, and the third a young lady. A solution of epi- nephrin hydrochloride, 1 : 1000, was given internally in 5-minim doses in water 3 times daily ^.j hour before food, and the treatment continued during 5 to 6 months with short in- tervals. The erythema almost en- tirely disappeared, and V/2 years after treatment it had not reappeared. No bad effect on the heart or blood- pressure was observed. Rothmann (Lancet; Charlotte Med. Jour., Oct., 1913). PITUITARY ORGANOTHER- APY. "We may assume," wrote Schafer in 1898, in a review of the investiga- tions on the physiological role of this organ, "that the pituitary body fur- nishes to the blood an internal secre- tion, and that this internal secretion tends to increase the contraction of the heart and arteries, and perhaps influ- ences nutrition of some of the tissues, especially bone and the tissues of the nervous system." Howell showed, how- ever, that of the two lobes of the organ extract of the anterior lobe produced no effect — a fact confirmed by several investigators — and that the main action of extracts of the posterior lobe was to slow the heart and raise the blood- pressure. Schafer and Vincent then 762 ANIMAL EXTRACTS (SAJOUS). concluded, after experiments, that the pituitary contained both a pressor and a depressor substance. The latter effect is increasingly being disregarded in practice, the posterior lobe, now offi- cial (U. S. P., 1916), giving rise to pressure effects. Doses of 15 to 20 minims of pituitrin produce a perceptible increase in the blood-pressure in from four to twenty minutes, and maintain it from twenty minutes to an hour or even longer, differing in this respect from adrenalin, in which the effect is far more tran- sient. There is a coincident change in the pulse rate, diminishing as the blood- pressure increases and increasing as it falls. However, this change is more gradual, both in its downward course and its return to normal. The rise in blood-pressure varies from 8 to 38 mm., while the pulse rate falls from 4 to 17 beats per minute. No untoward effects were noted in any of the cases in which larger or repeated doses were administered. The inhibi- tory influence upon the pulse is more lasting than the influence upon the blood-pressure. H. G. Beck and J. J. O'Malley (Amer. Med., Oct., 1909). In animals intravenous injections of pituitrin in small dosage can be repeated at intervals of 10 or 15 min- utes without significant failure of their pressor effect in animals. In either the dog or cat occlusion of the adrenal circulation does not diminish the pressor effect of a standard dose of pituitrin. There is probably, therefore, no direct de- pendence on adrenal functioning upon pituitary secretion. Hoskins and McPeek (Amer. Jour. Physiol., Sept. 2, 1913). The effect of pituitary extract on the human blood was by no means found uniform by the writer, and did not correspond to the striking re- sults obtained in animal experimenta- tion. As previously shown by von der Velden, pituitary extract caused no constant rise in blood-pressure and no change in the pulse-rate or in the respirition-rate. Nor was there any special effect on the general sys- tem. Behrenroth (Deut. Archiv f. klin. Med., cxiii, Nu. 3-4, 1914). The pressor substance was looked upon as resembling that of adrenal ex- tracts, its application to mucous mem- liranes producing blanching, as is the case with adrenalin. With Herring, Schafer then found that pituitary ex- tract was endowed with powerful di- uretic properties, and that it produced dilatation of the organ. Finally, Her- ring advanced the theory that the se- cretion was formed in tlie anterior lobe and completed in the posterior lobe, and that it then passed into the third ventricle, to mix therein with the cere- brospinal fluid. From my viewpoint, the prevailing idea that either lobe of the pituitary is a secreting organ was based on an assumption at the start, and has been perpetuated as such. The effects of its extracts are those of the adrenal prin- ciple which the posterior pituitary con- tains ; not only does the pressor sub- stance give the actions of chromaffin substance, due to the presence of the adrenal principle, but it produces the same effects. The functions I have at- tributed to the pituitary are totally dif- ferent ; but as they do not bear in any way upon the valuable therapeutic ef- fects of this organ, they need not be described in the present connection. As I view it, therefore, pituitary prepara- tions merely afford an additional and efficacious way of administering adre- nal preparations. Being bound up in organic combination, the adrenal prin- ciple acts with leas violence, owing, probably, to the fact that even in the tissues, after the pituitary preparation has been injected, tl.e product is de- composed very slowly. ANIMAL EXTRACTS (SAJOUS). 763 The writer found that extract of suprarenal and pituitary glands had a rapid and marked effect as pupil dila- tors. Thyroid had no mydriatic effect. Catapano (Deut. med. Woch., Jan. 31, 1911). Comprehensive experiments in dogs led the writers to conclude that pituitrin injected intravenously caused a moderate rise of the blood-pres- sure, slowing of the pulse rate, and a temporary arrest of the urinary ex- cretion, without true secondary poly- uria. The rise in blood-pressure is more marked when the normal tonic activity of the vagi has been sus- pended or the terminations of this ner e paralyzed. It is due to a vis- ceral and peripheral vasoconstriction, which appears to occur independently of th^ general vasomotor center. The diminutior of uri lary excretion pro- duced by pituitrin is dependent upon a renal vasoconstriction which seems to be of peripheral origin. In the whole animal the action of adrenalin is exerted in the same direction as that of pituitrin, but is more power- ful and also more evanescent. It dif- fers from pituitrin in increasing the amplitude of. and accelerating the contractions of, the isolated heart. Beco and Plumier (Bull, de I'Acad. de Med. de Belg., xxvii, No. 5, 1913). Pituitary extracts, when prepared by certain methods, yield color re- actions suggesting epinephrin or an epinephrin-like compound. The phys- iologic actions of such solutions can be explained by the presence of such a compound, modified by admixed substances. That epinephrin has not yet been isolated from these glands may be due to the small amounts present. Watanabe and Crawford (Jour, of Pharmacol, and Exper. Therap., Jan., 1916). Whichever opinion ultimately pre- vails, the fact remains that pituitary is a valuable remedial agent in many disor- ders. Its marked advantage is that it sustains the rise of blood-pressure, to which it gives rise much longer than does adrenalin, thus being more re- liable in shock and other emergency cases. It seems also to sustain the tem- perature and the muscular tone, car- diac, vascular, intestinal, and uterine, longer than the adrenal active principle. It possesses also a great practical ad- vantage over adrenalin and other adre- nal principles in that it can be admin- istered by the mouth without compro- mising its effects. At the present writing (1921) pitui- tary preparations (posterior lobe) are looked upon as capable of raising the blood-pressure, of enhancing the con- tractile power of the uterus, and by dilating the renal vessels of producing diuresis. PREPARATIONS AND DOSE. — Pituitary gland is available in drug stores in the form of powder or tablets of desiccated gland. The new U. S. P. (1916) has made official a powder {hy- pophysis sicca) of the posterior lobe, the active one therapeutically, the dose of which is ^^ grain (0.03 Gm.). The prevailing tendency is to give too large a dose of pituitary. I have seen very hamiful effects produced by such medi- cation. I seldom prescribe over %o grain (0.006 Gm.) three times daily. A product called "pituitrin" by its manufacturers, in the form of a solu- tion, is available on our market for oral or intramuscular use, the dose of which is given as 10 to 30 minims (0.66 to 2 c.c). There is also a liquid extract of the posterior lobe, wrongly termed "infun- dibular extract," the infundibulum be- ing the pedicle which unites both lobes of the pituitary to the base of the brain. This infundibular extract affects mucous membranes precisely as do adrenal extractives, and should be ap- plied only when diluted in eight or ten 764 ANIMAL EXTRACTS (SAJOUS). times the same quantity of saline solu- tion. It may be given orally in 10- to 30- minim (0.62 to 2 c.c.) doses, or intramuscularly in 3- to 15- minim (0.2 to 0.92 c.c.) (loses. Liquor hypophysis, U. S. P. (solu- tion of hypophysis), is a preparation containing the water-soluble principles from the fresh posterior lobe of cattle. It is standardized for uterine activity on the isolated uterus of the virgin guinea-pig, and is officially required to be kept in a sterile condition in glass containers. Dose, 5 to 15 minims (0.3 to 1 c.c). An important addition to our pituitary pharmacological agents was made re- cently by Prof. T. B. Robertson of the University of California and now of the University of Toronto. He terms tethelin a sul)stance isolated in relatively pure form from the anterior lobe of ox pituitary. It was found to retard the early growth of animals, but to markedly accelerate post- adolescent growth. The animals receiving it were smaller but heavier than controls, and showed favorable effects on their skins. Animals deprived of food for a time and then given unlimited food, re- gained weight more rapidly when given tethelin than controls. It stimulated the healing of wounds. The substance has marked powers in influencing the growths of tissue. It was given orally and hypo- dermically with the same results. THERAPEUTICS. — Acromegaly. — The possible value of pituitary ex- tracts here suggested itself, but, al- though a few of the symptoms, the headache, lethargy, and amnesia, were relieved in some, no cures were ob- tained. Analysis of the cases reported benefited suggests an explanation apart from the organ as the source of an in- ternal secretion, but entirely in keeping with the presence in the pituitary prep- aration of adrenal secretion in organic combination. IMarinesco observed that it was the extremely violent headaches that were relieved, there being no benefit otherwise, excepting perhaps increased diuresis. Kuh, obtaining no favorable result, withdrew the remedy, but the patient begged to be given the powders again, having found his headache much more intense when he failed to take them. The same observation had been recorded by Cyon, the patient, an obese child of 12 years, having besides lost twenty pounds in weight. What benefit was obtained in 1 case out of 7 cases treated by Kinnicutt was also limited to the headache and neuralgia. Les- zynsky, after a prolonged trial in 2 cases, wrote: "While some published reports as to the efficacy of the prep- arations of the sheep's gland have seemed quite encouraging in so far as the relief of headache and of paresthesia of the hands is concerned, it is the general consensus of opinion that it in no way influences the progress of this disease." Still, the relief of the headache and paresthesias indicates some potent ac- tion. This is accounted for if the adre- nal principle is considered as the active agent of the pituitary preparations, since, as Langley has shown, it is prin- cipally upon the arterioles that the adrenal principle acts, a view which has now become classic. Such being the case, the tumor of the pituitary, or the compressed tissues around it, re- ceive less blood through their con- stricted arterioles, and the sensory ter- minals of the peripheral likewise. The resulting ischeinia of these tissues thus accounts for diminution of pain — as long only as the remedy is administered. Cardiac Disorders. — As shown by Renon and Delille, pituitary gland raises the depressed arterial tension and corrects purely functional disorders of rhythm. ANIMAL EXTRACTS (SAJOUS). 765 It is recommended in doses ranging from 3 to 6 grains (0.2 to 0.4 Gm.) of the whole gland in myocardial weak- ness, particularly in that due to infec- tions when the blood-pressure is reced- ing, the pulse is becoming more rapid, and the urine scanty. While less active than digitalis as a diuretic, it, neverthe- less, serves a valuable purpose in this connection. It is advantageous in mi- tral disorders when there is hyposys- tole and in chronic myocarditis, par- ticularly that due to alcoholism. It is also useful in the tachycardia of certain neuroses and during meno- pause. These results have been con- firmed by Trerotoli, Parisot, and others. It is contraindicated in aortic affec- tions in any disorder in which high vas- cular tension prevails, and where there is a tendency to anginal pains, which it tends greatly to aggravate. Pituitary gland is preferred to adre- nal preparations and particularly adren- alin when the action is to be sustained, the former being useful in urgent cases. Renon and Delille, however, prefer digitalis, and recommend pituitary gland only when the latter fails. Leon- ard Williams, on the other hand, deems it superior to digitalis, strophanthus, strychnine, and other classic tonics in what he terms the "runaway heart of toxic states," influenza, pneumonia, bronchitis, etc., with tachycardia, but low blood-pressure, and in all cases in which there is posttoxic cardiac debil- ity. In these cases — which, from my viewpoint, are instances of pure hypoa- drenia — Williams regards pituitary preparations superior to any remedy at our command. In heart-failure and shock, it has been highly recommended, 15 minims (0.92 c.c.) of the extract being injected intramuscularly. While its virtues would seem to recommend it for the perpetuation of the effects of adrena- lin, which are, at best, but temporary, the number of cases in which it has been tried has been too limited so far to warrant an opinion as to its actual value. In 3 cases of heart-failure during anesthesia the writer injected 1 c.c. of a 20 per cent, sohition of the poste- rior lobe of the pituitary body intra- muscularly. The effect was almost immediate, and the almost impercep- tible pulse soon became large and bound- ing. This effect lasted from twelve to sixteen hours, and gradually passed off. Not only did the pulse become larger in expansion, but it was also slowed, and, whereas it had been irregular, it became regular. This effect seems due not only to the action of the drug on the blood-vessels, but also on the heart. The injection was given in conjunction with normal saline by rectum. G. G. Wray (Brit. Med. Jour., Dec. 18, 1909). The benefit which follows the use of pituitrin by intramuscular injection when the blood-pressure is abnormally low is very marked. The writer recom- mends it especially for threatened collapse and hemorrhage after child- birth. He thinks it may prove of value in surgical shock and in acute febrile states, but his use of it in these cases has not yet been exten- sive. Pituitrin has two advantages over adrenalin: namely, its action is moderate and prolonged. Klotz (Munch, med. Woch., May 23, 1911). While the treatment of low blood- pressure in infectious diseases by in- jections of adrenalin is very success- ful, it is not perfectly satisfactory, Staub having shown that only 6 per cent, of the drug reaches the circulat- ing blood, while the remainder is disintegrated at the site of injection, while large doses may cause suppura- tion, and even extensive necrosis of the skin at the site of injection and also glycosuria. The author has, therefore, substituted pituitrin on ac- '66 ANIMAL EXTRACTS (SAJOUS). count of its powerful action on un- striated muscle. H. von Willebrand (Finska laekere Handl., vol. liv, 1912). The writer recommends pituitrin in acute heart failure with dilatation. Too large a dose may in the aged result, however, in a sudden harmful rise of pressure. This may entail hemorrhage and apoplexy. A weak- ened and tired-out myocardium may be rapidly reduced to a normal size. E. Zueblin (Boston Med. and Surg. Jour.. Dec. 24, 1914)). After using posterior pituitary (pituitrin) in over 1000 cases with cardiovascular and metabolic atony and deficient defensive activity the writer regards pituitary therapeutics as easily the most effective resources at our command in organotherapy. R. A. Bate (Louisville Mthly. Jour, of Med. and Surg., Sept., 1915). Obstetrics. — Dale found, in the course of comprehensive experiments, that (in keeping with that of the adre- nal principle) the action of extract of pituitary was "a direct stimulation of involuntary muscle without any rela- tion to innervation." Frohlich and Frankl-Hochwart then ascertained that it caused contractions of the pregnant uterus in rabbits, while Foges and Hof- statter resorted to this property in so far as the human uterus was concerned to check post-partum and other uterine hemorrhages, the test including 63 cases. The extract proved worthless by the mouth; but when injected intra- muscularly, marked uterine contraction appeared within five minutes and lasted a long while in most cases. It is espe- cially efficient in placenta praevia, particularly after version and expul- sion of the fetus, removal of the placenta is accompanied by profuse hemorrhage. It is also useful in cases of normal labor followed by hemorrhage or uterine relaxation. In 63 cases of post-partum hemor- rhage and after 1 abortion the intra- muscular injection of pituitrin (in doses of 1 to 2 c.c.) proved superior to ergotin with reference to the intensity of the contraction and continuance of the excitability. The authors were en- abled to note the effect of pituitrin particularly in 6 cases of extraperi- toneal Cesarean section. "After not more than five minutes one could see how the exposed uterus contracted, in response to a light tactile irritation, to a firm ball. The action continued for a long time, which accounts for the fact that there was no hemorrhage, a com- plication that is always feared in con- nection with Cesarean section." In accordance with their observations, the authors are of the opinion that there is no doubt concerning the specific effect of pituitrin upon the excitation of the uterus. Foges and HofstJitter (Zen- tralbl. f. Gyniik., Nu. 46, 1910). Pituitary liquid in placenta previa, in y> c.c. (8 minims) dosage, with advisable repetitions during the latter part of the first stage, and a single large dose (1 to V/2 c.c. — 16 to 24 minims) when dilatation is complete, is recommended by the writers, their results having been uniformly good. Gallagher and Gallagher (Surg., Gynec. and Obstet. ; Amer. Med., Dec, 1916V Small doses of pituitary extract without any curettement or packing are recommended by the writer in incomplete abortion and placenta previa. lie usually gives K' c.c. (8 minims) pituitary liquid hypoder- mically daily or every other day until the placenta is expelled. This oc- curred in most cases in 2 or 3 days and in but 1 in 5 days. The bleeding during the time does not exceed that of an ordinary menstrual period. Lipkins (X. W. Med., Mar., 1918). The trend of recent clinical observa- tions is that if pituitrin is used at all in obstetrics, it should be in smaller doses even in cases of uterine inertia, full doses exposing the uterus to rup- ANIMAL EXTRACTS (SAJOUS). 767 ture and the fetus to asphyxia. It is especially dangerous in primipars. A case was observed in which after evacuation of the uterus after abor- tion, pituitary and ergotin were given for hemostasis. The pulse became very poor and soon afterwards the woman collapsed. Hemorrhage had wholly ceased. Intravenous saline in- fusion alone produced a reaction, but only after some hours. The condi- tion is best explained by synergism of 2 drugs which alike cause excessive contraction of the blood-vessels facilitated by the great loss of blood. Bovermann (Miuich. med. Woch., July 9, 16, 1912). The following complications have followed the use of pituitary extract in labor cases: Post partum uterine atony, fetal asphyxia, maternal col- lapse, eclamptic convulsions, tetanus of the uterus, premature placental separation and rupture of the uterus. In his own experience uterine tetanus followed as little as 5 minims (0.3 c.c.) of the extract in 2 instances. A greater tendency to tetanus in primi- parae than in multiparfe was noticed, and in many instances restoration of normal contractions did not follow, a low forceps operation becoming necessary. Fetal asphyxia was like- wise noted in many primiparae, though never fatal. Post partum atony, with alarming hemorrhage in several cases, was noted particularly in prolonged labor and in multiparpe in whom sev- eral pregnancies had occurred in rapid succession. The drug has no place in normal obstetrics. L. G. McNeile (Amer. Jour, of Obstet., Sept., 1916). Within 12 weeks of each other there had been admitted to the ob- stetric ward of the Delaware Hos- pital 2 patients with spontaneous rup- ture of the uterus, following the ad- ministration of a single dose of 1 c.c. (16 minims) of pituitary solution. They had met the usual indications for the use of pituitary solution. Both pelves were practically normal and the conjugata vera, as estimated at operation, at least 10 cm. in each. But l)Oth babies were found to be somewhat above the average size, one weighing a little above and the other a little below 4500 Gm.— 9.9 pounds. One patient died, the other recovered. W. Wertenbaker (Jour. Amer. Med. Assoc, Ixviii, 1895, 1917). After testing pituitrin in a large number of labors, the writers advo- cate very small doses by the intra- muscular injections, their average dose being 2 to 4 minims (0.12 to 0.25 c.c), and in labor at term ex- clusively— never for the induction of abortion or premature labor, where it fails entirely. It is only indicated after the onset of labor for strength- ening the uterine contractions; also in combination with castor oil for the induction of labor at full term. These small, entirely harmless doses of pituitrin serve to reduce the need for the application of forceps, thus causing otherwise instrumental de- liveries to terminate like normal pro- gressive labors. Stein and Dover (Med. Rec, Aug. 11, 1917). Analyses of the reports of 5245 cases of labor in which pituitrin was used strikingly emphasized the fact that the contents of 1 ampoule (15 minims — 1 c.c.) is much too large a dose and that this should be reduced to Yz of that dose, which may be re- peated at intervals of 30 to 50 min- utes if necessary. The first dose is usually decidedly more effective than the subsequent ones. The field of usefulness for this drug is sharply limited. This is secondary inertia late in the second stage in multip- arous women who have had previous unobstructed labors, a normal presen- tation, fully dilated cervix, head moulded and through the brim, mem- branes ruptured, and perineum re- laxed. In such cases its use fre- quently avoids a low forceps opera- tion. An anesthetic should be given when the action of the pituitary ex- tract begins, and one should always be prepared to complete delivery with forceps. It is inferior to ergot for the control of postpartum hemor- 768 ANIMAL EXTRACTS (SAJOUS). rhage. It should never be used in normal labor and it is dangerous in primiparje. Its use should invariably be preceded by accurate pelvimetry. In the cases analyzed there were 20 of rupture of the uterus, 12 in the last year in a total of 1293 cases in which the drug was used. This gives 1 in each 106 cases. The danger to the fetus has increased during the past year, probably owing to the more reckless use of large doses. During 1914 there were 27 fetal deaths in 3952 cases, or 1 in 146 cases, while during 1916 there were 34 fetal deaths in 1293 cases, or 1 in every 38 cases. Dangerous fetal asphyxia is even more frequent. It is quite obvious that the field of safe usefulness of pituitary solution is very sharply limited and any transgression is fraught with considerable danger. J. J. Mundell (Jour. Amer. Med. Assoc, June 2, 1917). Indications for use of pituitrin are limited to simj^le uterine inertia in multipara; without fetal or maternal dystocia and in patients not exhausted. The author's personal experience and observations of cases referred to the Lying-in Hospital, had led him to add his own to the warnings already published. Pituitrin in Cesarean sec- tion is not as certain as ergot. It is merely an aid to forceps in certain cases of dystocia where stimulation of the uterine contractions might drive the head to a more suitable level for instrumental delivery. Pitui- trin was of especial value in curettage for incomplete abortion, also useful in metrorrhagia of young girls and in older women with small fibroids or inflammatory lesions in the adnexal regions resulting in hyperemia. G. W. Kosmak (Trans. Amer. Med. Assoc; N. Y. Med. Jour., June 29, 1918). The writer has long opposed the use of pituitary in labor. Further experience has confirmed the opinion. Rupture of the uterus and laceration of the cervix has followed improper use of the drug. Asphyxia of the newborn has been caused and the en- docrinal relationships of the fetus have been disturbed. As to the use of the drug in cases of Cesarean section, it should not be given after the sutures were put in, as the sudden contraction may tear the sutures out, and peritonitis follow. In true pri- mary inertia with or without rupture of the waters pituitrin may do good. J. B. DeLee (Trans. Amer. Med. Assoc; Med. Rec, June 22, 1918). In 3 cases of intestinal paresis fol- lowinjT;- operations for ovarian cyst and ectopic gestation, quite prompt relief was obtained by injections of pituitary extract. In a case of subinvolution of the uterus, the pa- tient suffering from menorrhagia, for which she had recently been curetted without result, and having soft, flabby tissues and low blood-pressure, Aarons decided to try the effect of repeated doses of pituitary extract. Six injec- tions were given in as many weeks. The uterus underwent contraction from 5 to 3 inches as measured by the sound ; the general condition was much improved, and had remained so six months after the treatment. During the administration of the pituitary ex- tract marked polyuria was noted. No deleterious effects resulted. The author suggests, however, that the use of the extract in subinvolution be limited to cases with associated low blood-pres- sure. Ott and Scott found infundibulin, i.e., extract of the posterior lobe, to act as a powerful galactagogue in the goat. In practice its use has at least given rise to a temporary increase of secretory activity. The writers found that pituitrin not only increased the quantity of milk secreted, but also that it became rich in fats, although this increase is only temporary. The increase in quantity is not so marked, however, after sub- ANIMAL EXTRACTS (SAJOUS). 769 sequent doses. Hill and Simpson (Amer. Jour, of Physiol., Oct., 1914). Pituitrin was found to increase muscular activity, leading to con- striction of the milk ducts and alveoli of the active mammary gland, with a consequent expression of milk. This action prevailed also on the excised gland in the absence of any circula- tion. The flow of milk produced by pituitrin is dependent on the amount of milk present in the gland. There is no evidence of any true secretory action. The non-lactating gland, up to a late stage of pregnancj\ is not sensitive to pituitrin. Gaines (Amer. Jour, of Physiol., Aug. 1, 1915). As a galactagogue the writer em- ploys pituitary extract by mouth with as great confidence as he does ergot to cause uterine contraction after labor. He has noted no unpleasant phenomena from it. Its action proved permanent. H. C. Hughes (Therap. Gaz., May, 1915). Infectious Diseases. — In this gen- eral class of disorders the use of pit- uitary acts, from my viewpoint, and in keeping with the effects of adre- nal preparations, by enhancing the im- munizing activity of the blood and the tone of the cardiovascular system. That such was the case in the infec- tious diseases in which it was tried can only, however, be surmised. Adrenalin and pituitrin were used in combination in cases of marked circulatory disturbances characterized by depression in children in pneu- monia, diphtheria, and typhoid. He injected 0.25 c.c. (4 minims) of a 1 : 1000 pituitrin preparation and 0.5 c.c. (8 minims) of a 1 : 1000 adrenalin solution in young children, and double the dose in older children, repeated every 6 hours, about the duration of the rise of blood-pressure. In the interval camphor or cafTeine was injected. P. Rohmer (Miinch. mad. Woch., June 16, 1914). The writer studied the efifects of pituitary injections on blood-pressure of febrile patients in 15 cases, 6 of whom had pulmonary tuberculosis, 3 infectious sore throat, 1 exophthal- mic goiter, 3 lobar pneumonia, 1 sur- gical shock, and 1 convalescing from typhoid. From 1 to 1.5 c.c. (16 to 24 minims) of extract of pituitary gland was injected deep into the muscle of the arm. The blood-pres- sures were taken several times be- fore the injection, and thereafter at intervals of about 15 minutes for 1 hour or more. The pulse rate, tem- perature and rate of respiration were also noted. Aside from an occasional slowing of the pulse rate, which never exceeded 10 beats per minute, no definite change in these occurred. The rise in the diastolic pressure amounted in some instances to 15 mm. Hg. or more, and this, together with its time and relative constancy, made it certain that it was due to the action of the drug. Schmidt (Arch. Internal Med.. June, 1917). Renon and Delille found that in typhoid fever it raised the blood- pressure, slowed the pulse, increased diuresis, and improved the patients in general, hastening convalescence no- ticeably. In diphtheria, in which the toxin reduces the vascular tension and promotes cardiac complications, it lowered the pulse rate, raised the blood-pressure, and increased diure- sis. In erysipelas it seemed to hasten the favorable evolution of the disease. In pneumonia it raised the blood- pressure when this became low, but without influencing favorably the evo- lution of the disease. In broncho- pneumonia, however, the opposite proved to be the case, considerable benefit being noted. Influenza was found to be very favorably influenced, rapid recovery resulting in patients aged, respectively, 80 and 63 years. This was confirmed by Azam, in the infectious form. Renon and Azam enumerate the phenomena which, in in- 1-49 770 ANIMAL EXTRACTS (SAJOUS). fectious diseases, indicate the need of pituitary: 1, a fall of the arterial ten- sion ; 2, quickening of the pulse and, as complementary minor phenomena, insomnia, anorexia, abnormal sweating, and heat flushes. Under the influence of pituitary there occur: 1, increase of arterial tension ; 2, slowing of the pulse, with increase of power and amplitude ; 3, increased diuresis ; 4, increase in weight ; 5, hastening of convalescence. In several cases of tuberculosis treated by Renon and Delille, the re- sults were not, on the whole, encour- aging. In a case of Addison's disease complicating tuberculosis, however, there was a notable rise of the blood- pressure and diminution of the asthe- nia. Trerotoli had already noted the beneficial efl'ects of pituitary body in Addison's disease — a fact which fur- ther suggests that the active agent of pituitary substance is its adrenal com- ponent. Exophthalmic Goiter. — Renon and Delille obtained considerable improve- ment in this disease by the use of pitui- tary gland. From the fourth to the fifth day, the sleeplessness, tremor, di- gestive disturbance, sweating, and sen- sation of heat were considerably les- sened. The tachycardia improved less rapidly, the pulse becoming slower gradually and attaining its slowest rate toward the fifteenth day. The arterial tension also rose steadily, attaining the maximum toward the third week, fall- ing again somewhat, but not to the for- mer low level. Some diminution of the exophthalmus occurred, but the goiter was not reduced. The dose adminis- tered was 414 grains (0.30 Gm.) of the whole pituitary (ox) gland daily, a dose which they deem advisable to in- crease to 714 grains (0.50 Gm.) in di- vided doses daily. The symptoms tend to return, however, on discontinuing the remedy. Cases subsequently treated were also benefited, but no cures were effected. It is well to remember in this connection that the dose of the dried pituitary available in this country is but 2 grains. This mode of action, from my view- point, corresponds precisely with that referred to under the preceding head- ing. We have seen that the main pathological condition — that to which all the prominent symptoms of exoph- thalmic goiter were due — was a gen- eral dilatation of the arterioles. Pit- uitary extract causing constriction of these vessels as long as it is admin- istered, it offsets for the time the morbid phenomena enumerated. That such is actually the case was demon- strated by Hal lion and Carrion, who found, experimentally, that pituitary extracts "always produced their ef- fects by raising the arterial tension," producing at the same time "an in- tense vasoconstrictor action upon the thyroid body." Briefly, we have here precisely the physiological action nec- essary, the vasoconstrictor power of the adrenal component of the pitui- tary gland superseding the vasodila- tor action of the thyroid, the under- lying cause of the disease. Nervous and Mental Diseases and Myopathies. — Renon and Delille used pituitary in 10 neurasthenics in whom tachycardia; irregular vascular tension, often below normal; a sensation of op- pression, myasthenia, insomnia, and anorexia were present. In these cases 3 to 5 grains (0.2 to 0.3 Gm.) daily proved remarkably useful, though no complete recovery was noted. This dose refers only of course to the whole gland. Delille and Vincent obtained a com- ANIMAL EXTRACTS (SAJOUS). 771 plete recovery in a grave case of bulbospinal myasthenia by the simul- taneous use of pituitary and ovarian extracts. Parhon and Urechia and Leopold-Levi and de Rothschild had also obtained favorable results with pituitary in similar cases. Browning observed good efifects in cases of chorea in which this disorder occurred in conjunction with stunted growth, as shown under the next heading. In epilepsy it was tried by ^lairet and Bose, but only served to increase the number of attacks — a result to be expected, since Spitska has shown that these were due to abnormal elevation of the blood-pressure. In some in- stances it provoked delirium. Sollier and Chartier tried pituitary in mental disorders and found it useful in depressive states. It raised the blood-pressure, reduced the pulse, sup- pressed profuse sweating, and improved the asthenia. The synthesis of percep- tions and the association of ideas were improved, and mental operations were incited more promptly. Stunted Growth and Imbecility. — In a case in which a child of 3 years had shown the evidences of hypothy- roidia with idiocy sufficiently to sug- gest the use of thyroid, Leopold-Levi and de Rothschild found this agent use- less. The case being attended with marked myasthenia, they adminis- tered pituitary extract, 1% grains (0.1 Gm.) twice daily, which corre- sponded with 7^ grains (0.5 Gm.) of the fresh gland. Marked signs of im- provement appeared within a few days. The intelligence developed to a remarkable degree, and soon reached that of a child of a corresponding age, 3 years, though before the treatment it did not exceed that of a 7 or 8 months' infant. Two similar cases, one of which showed symptoms of Little's disease, were similarly bene- fited. Browning used pituitary only in undersized or backward children and youths (not real dwarfs or midgets), and obtained results both as height and weight in 4 cases described. The newly discovered tethelin is thought to have special properties in this direction. The daily addition of 50 to 75 Gm. (1% to 2>2 ounces) of fresh desic- cated defatted anterior lobe of the ox to young dogs failed, except in some instances, to stimulate their growth as evidenced by their weight. Nor was their growth impeded. In white rats (Amer. Jour, of Physiol., Nov., 1912) the same investigator noted the inability of anterior lobe to stimulate growth. In fact, it seemed to impede growth. T. B. Aldrich (Research Lab. P., D. & Co., vol. i, 1913). The writers, in experiments in ani- mals, the gland being given in suffi- cient amounts to represent the relative weight of an average man, found that ''neither anterior nor posterior lobes had any effect on the weight or growth of the animal." Lewis and Miller (Arch, of Med., Aug. 15, 1913). The growth of 3'oung fowl was re- tarded by the addition to the diet of fresh, unmodified anterior lobe of ox pituitary, as shown both in body- weight and in length of the long bones. Involution of the thymus ac- companied this retardation and may have borne a causal relation to it. These effects are more marked in the males than in the females. R. Wul- zen (Amer. Jour, of Physiol., May, 1914). A striking fact in the therapy of cretinism is that symptoms due to hypothyroidism clear up under pitui- tary gland. In a personal case there was a striking change in the contour of the hands, ankles, hips, buttocks, thighs and shoulders that could be made to appear or recede by giving or taking away pituitary gland. The 772 ANIMAL EXTRACTS (SAJOUS). effect on the child's disposition was also striking. R. S. Haynes (Jour. Amer. Med. Assoc, June 19, 1915). The effect of giving 4 mg. (Vic grain) of tethelin per day by mouth to mice for from 5 weeks onward, was found by the writer to be similar to that of pituitary tissue, viz., initial retardation of growth, followed by acceleration. Both effects were so exaggerated, however, as to involve total distortion of the curve of growth, the second growth-cycle being enormously prolonged, the third abbreviated and accelerated. T. B. Robertson (Endocrinology, Jan., 1917). Intestinal Paresis. — Bell and Hicks have found pituitary extract of value in paralytic di.stention of the intestines. It never failed either in postoperative or other paresis if given intramuscu- larly when the intestine begins to dis- tend in 15-ininim doses (0.92 c.c), re- peated in an hour if required. The effect is then sustained by daily doses if need be. The beneficial influence of the injections was, as a rule, noticeable in a few minutes. Twenty-one cases illustrating the fact that pituitary extract has a very marked effect upon the muscular coats of the bowel, and that it is able to overcome the temporary paralysis due to ex- posure after abdominal operations. This is shown by the early passage of flatus and by the absence of ab- dominal discomfort. In only 3 cases did the bowels act without the assist- ance of the enema, but in every case except 2 a satisfactory action of the bowels was obtained after a simple enema, and it was unnecessary to give any aperient by the mouth. L. A. Bidwell (Clinical Journal, Sept. 6, 1911). In postoperative cases, often as a routine procedure, the writer found pituitrin very beneficial in starting in- testinal activity as an aid to enemata or drugs given by mouth; repeated hypodermic injections often overcame symptoms simulating intestinal par- esis. S. W. Bandler (Med. Rec, Feb. 12, 1916). Good results were obtained by the writer from pituitary extract in the cases of intestinal paralysis fre- quently following operations for acute appendicitis with general peri- tonitis. In some of these intestinal paralysis is the only manifestation of the peritoneal inflammation, and at times the patient's life might be saved if the paralysis were overcome. In a case of gangrenous appendicitis in a child of 10 years, with marked abdominal distention and absence of bowel movements for 6 days after the operation in spite of gastric lavage, enemas, and castor oil suppositories, a first subcutaneous injection of 1 c.c. (16 minims) of pituitary extract (posterior lobe) brought colicky pains and a small stool within IS minutes. Further injections on subsequent days were promptly followed by in- creasingly copious bowel movements, and recovery took place. In another case, that of a soldier suffering from intestinal occlusion, whose bowels had not moved 16 days, equally good results were obtained. E. Kirmisson (Bull, de I'Acad. de med., Jan. 29, 1918). To prevent postoperative nausea, vomiting, and gas pains following ab- dominal operations the writers recom- mend pituitrin hypodermicallj'. The method used is as follows: Mor- phine, y^s grain (0.01 Gm.) and atro- pine, Viso grain (0.00035 Gm. ), hypo- dermically 1 hour before operation. Immediately after operation they give 1 c.c. (16 minims) of pituitrin hypo- dermically. This same dose is re- peated in 2 hours. Two hours later, Vz c.c. (8 minims), and 4 hours later another K' c.c. (8 minims). Where too much handling of the viscera has not occurred, no more pituitrin is given, but in severe operations, doses of Yi c.c. (8 minims) are continued every 4 hours for 24 hours. They give 3 grains (0.2 Gm.) of calomel in 54-grain (0.032 Gm.) doses every V2 hour, followed by a saline cathartic. ANIMAL EXTRACTS (SAJOUS). 17Z On the basis of 126 cases, of which 104 were non-septic, 22 septic, and 9 cases of eclampsia, the writers con- clude as follows: (1) Pituitrin is a valuable drug in stimulating the mus- cular coat of the intestine after ab- dominal section in non-septic cases. (2) It is of decided aid in preventing postoperative shock in non-septic cases of abdominal section, as evi- denced by lack of rise of tempera- ture or pulse-rate. (3) It does not appear to have any influence in cases complicated with septic peritonitis. (4) It stimulates the secretory activ- ity of the kidneys in eclampsia. (5) It materially reduces the postopera- tive suffering. Davis and Owens (New Orleans Med. and Surg. Jour., Ixx, 712, 1918). Pituitary gland is also of value in the intestinal paresis following pelvic op- erations. ORCHITIC OR TESTICULAR ORGANOTHERAPY; SPERMIN. The mode of action of these agents has not as yet been explained otherwise than by the process I have suggested, viz., that it is similar to that of the adrenal products, owing to the pres- ence in these preparations of the adre- nal principle. That the testicle influences power- fully the organism at large is well shown by the fact that castration be- fore puberty modifies in many partic- ulars the development of the individual. They preserve to a certain extent the characteristics of infantilism, the skin remaining soft and white, their muscles flabby and weak, and the voice high- pitched. Yet they are usually tall, ow- ing to inordinate growth of the bones. They lack courage, initiative, and in- telligence. It is evident, therefore, that the testicles do not solely carry on gen- ital functions. Brown-Sequard, in fact, taught that they carried on a dual role : 1, procreation; 2, the production of an internal secretion which stimulates and sustains the energy of the nerve- centers and cord, and capable, more- over, of endowing the individual with physical, moral, and intellectual char- acteristics of sex. His own physical and intellectual activity having been greatly improved at the age of 72 years, by injections of an extract prepared from the testes of young dogs, he con- cluded that it possessed marked thera- peutic value. No one who, as I did, saw Brown-Sequard before and after he had submitted himself to this treat- ment could stretch his imagination suf- ficiently to attribute the change in his appearance to autosuggestion. He lit- erally looked twenty years younger. Unfortunately, the value of testicular preparations was exaggerated by many observers to such a degree that their use fell into disrepute, and the subject has received but little attention in re- cent years. The prevailing opinion at the present time is that the beneficial effects ob- tained from testicular preparations are not due necessarily to an internal secre- tion, though the existence of such is not denied, but to nucleoalbumins, sub- stances that are rich in phosphorus, re- sembling greatly lecithins and glycero- phosphates. In a eunuchoid studied by the writer the height was below the aver- age in relation to body weight, while lymphocytosis was insufficient. But there was no change in the sympa- thetic or autonomous excitability; the conditions of metabolism were normal; there was no disturbance of oxidation; no alimentary glyco- suria nor hydruria. E. Voelckel (Berl. klin. Woch., Apr. 15, 1918). A personal analytic study of the question brought out a suggestive 774 ANIMAL EXTRACTS (SAJOUS). fact, viz., that "spermin," which may be obtained not only from testicles, but from the ovaries of mammals and fish roes, presents the character- istics of the adrenal secretion, both as to composition and physiological action. As I pointed out in 1903 (see "Adrenal Extract," supra), the adre- nal secretion serves to take up the oxygen of the air and carry it to all parts of the body as the active constituent of hemoglobin. As such it sustains oxidation and metabolism. Now, Batty Shaw ("Organotherapy," 1st ed., p. 205, 1905) writes: "Spermin possesses the very curious property of being an oxygen carrier, and, according to Poehl, is responsible for those in- ternal oxidations which take place in the body-tissues. Again, I have urged that the adrenal secretion carries on its oxygenizing function catalytically as a ferment. Pantchenko (reprint from Trib. medicale, 1896) states that "spermin acts catalytically, thus in- creasing the oxidizing power of the blood, and simultaneously activates the intraorganic oxidation processes where these are weakened." More- over, as is the case with the active adrenal secretion, spermin gives the guaiac and Florence hemin test (Mari) ; it is, as a constituent of or- chitic extract, unaltered by boiling (Dixon) ; it increases the force and regularity of the heart much as does digitalis (McCarthy) ; it enhances the resistance to disease; it increases the production of urea ; it acts directly upon the cardiovascular system. More- over, as shown by Poehl — a fact which indicates that it is not specific to the testis — it is a ubiquitous constituent of the whole organism, in the female as well as the male. Poehl having found in 1895 (Zeit. f. klin. Med., Bd. xxvi, H. 1 u. 2) that spermin was present in all the differ- ent parts of the organism, it becomes a question whether its actual source is the testicle, as believed by him, or whether, as I hold, it is derived from tlie adrenals, the testicles being richly supplied with it only because of ihe importance of their functions, i.e., pro- creation. The relative importance of both sets of organs to life answers this question. If, as Poehl says, "it is the oxidizing action of spermin which plays the principal role in the phenom- ena it produces," the organs whose re- moval arrests oxidation sufficiently to render life impossible must be the source of the oxidizing agent. As is well known, removal of the testicles does not kill, while death invariably follows extirpation of both adrenals. It is plain, therefore, that the testicles do not produce the oxidizing substance shown by Poehl and others to be the active agent in spermin, and that it is the oxygen-laden adrenal secretion (adrenoxidase) it contains which en- dows it with therapeutic properties. On the whole, the foregoing facts have shown that, while, as held by Dixon, orchitic extract is a compound of phosphorus-laden bodies, nucleins, lecithin, etc., which acts much as do glycerophosphates and similar products (though containing spermin in rel- atively small quantities), spermin owes its beneficial effects to the fact that it is rich in oxygenized adrenal secretion, i.e., the product I have termed adren- oxidase. After much experimentation at the College de France, the writers were able to cause healing of extensive and deep wounds in a few days, by applying locally the pulp of sex glands procured by castrating young animals. The cells of these glands, ANIMAL EXTRACTS (SAJOUS). 775 through the secretion they contain and which is absorbed by the wound, exert an intense accelerating action on the process of granulation. The organ found most effectual in these experiments would, a priori, have been considered that most suitable, owing to its especial vital energy. Animals deprived of these organs are known to accumulate fat at the ex- pense of their muscles and to be- come apathetic and passive. In the wounds treated with this material, its use often had to be discontinued after a few days in order not to exceed the results sought and cause projection of new tissue beyond the level of the wound cavity by reason of a too in- tense development of granulations. With the aid of this treatment its sponsors hope to spare the wounded long months of suffering and con- siderably shorten their stay in hospitals. Voronoff and Bostwick (Presse med., Sept. 9. 1918). THERAPEUTICS.— The fact that testfcular preparations, including' spermin, have been recommended in a large number of disorders has not served to recommend them to the im- partial observer. The use of orchitic extract was extolled in various nerv- ous disorders, especially tabes, neu- rasthenia, melancholia, impotence, and paralysis agitans; in several cutane- ous disorders, eczema and psoriasis; in disorders of nutrition, gout, obesity, and glycosuria ; but others again have failed to obtain any favorable results. Spermin has also been recommended by Poehl and his followers not only in the majority of the foregoing dis- orders, but in many others besides, in acne, rheumatism, syphilis,marasmus, and in various infections, such as typhoid fever, diphtheria, and even cholera. It has been tried in Addi- son's disease, but adrenal prepara- tions are to be preferred. Emulsions of sex glands are avail- able sources of material for hormone therapy. The essential sex hormone is a powerful physiological cell stimulant and nutrient. The writer recommends it for the treatment of earh' stages of arteriosclerosis, nutri- tional diseases and certain functional neuroses. Lydston (Jour. Amer. Med. Assoc, May 13, 1916). In the light of the analysis submit- ted above, however, there is good ground for the belief that beneficial efifects were obtained in all these mala- dies. That the nucleoalbumins of orchitic extract, acting as would glyc- erophosphates, could be beneficial in the disorders enumerated, no one can deny. This can hardly be said, how- ever, of the cutaneous and nutritional disorders, unless the spermin the ex- tract contains, by enhancing oxidation and the destruction of toxic wastes, proves to be the active agent. Spermin itself — as adrenoxidase — is unquestion- ably capable of doing this actively, and in syphilis and marasmus of markedly enhancing the functional activity of all tissues. Again, the beneficial role of spermin in infections finds its expla- nation in a fact I have repeatedlv emphasized, viz.. that the oxygenized adrenal secretion, the active agent of spermin from my viewpoint, is an ac- tive participant in all immunizing processes, local and general. The main point to determine, how- ever, is whether orchitic extract or spermin aft'ords better or as good re- sults in any of the disorders enumer- ated than other remedies at our dis- posal. The evidence available indicates that such is not the case. Hence, the dis- use into which the testicular products have fallen. OVARIAN ORGANOTHERAPY. — The ovaries correspond in many 776 ANIMAL EXTRACTS (SAJOUS). ways with the testes in their influence upon general development : their re- moval in children causes them to grow up without feminine attributes ; absence of these organs prevents development of the uterus and the appearance of menstruation ; their removal after pu- berty arrests menstruation and leads to atrophy of the genital organs. These phenomena were attributed by Cura- tulo, in accord with Brown-Sequard's doctrine, to the loss of what influence an internal secretion supplied by the ovaries to the body at large possessed over its development. The administra- tion of ovarian substance in subjects deprived of their ovaries or during the menopause produced a marked amel- ioration of all distressing phenomena. The ovarian internal secretion be- ing elaborated by the interstitial cells the latter probably correspond to the lutein cells of the theca interna of the atresic follicle. The inter- stitial cells of the ovary are analo- gous to the testicular interstitial cells of Leydig, known to elaborate an in- ternal secretion. Hence ovarian ther- apy should include at least the prod- uct of the interstitial cells. Extracts of ovaries of pregnant animals, with exclusion of the corpora lutea, proved superior therapeutically to extracts of whole ovaries of non-pregnant animals which included the corpus luteum. W. P. Graves (Trans. Amer. Med. Assoc; N. Y. Med. Jour., June 30, 1917). The manner in which ovarian extract produces its effects has remained ob- scure. As Wilcox ("Pharmacology and Therapeutics," 7th ed., p. 824. 1907) says: "But little is known of its phar- macological action. Fresh ovarian ex- tract is said, when injected into the circulation in rabbits, to raise the blood- pressure, diminish the heart's action, and slow the respiration, and when ad- ministered to the human female also to increase the arterial tension. In the castrated animal it is found to increase oxidation to somewhat above the nor- mal degree, but on the normal animal it has no such effect." These are the identical efifects produced by adrenal preparations. From my viewpoint, it is, in fact, owing to the presence of this substance — not necessarily an in- ternal secretion — in the ovaries that they must be attributed. There exists, as shown by Schafer, a close homology between the interstitial of the ovary and the same cells in the adrenals ; both sets of organs are derived from the W'olfiian body; ovarian extract raises the blood-pressure and slows the heart, as shown by Federoff, Jacobs, and oth- ers. Removal of the ovaries, more- over, reduces the oxygen intake 10 per cent., as shown by Loewy and Richter, while ovarian extract restores it ; it lias been, therefore, regarded as an oxi- dizing ferment. Neumann and Vas noted that ovarian extract enhanced metabolism; Senator observed that ovarian preparations increased diuresis and the excretion of urea and phos- phoric acid. Its physiological effects are those of adrenal preparations, there- fore, in every respect. Its effects on oxidation are so strik- ing, in fact, that they have been clearly recognized by many clinicians. "We are authorized to classify ovarian organotherapy among the oxidizing agents," write Dalche and Lepinois. "This conclusion, it must be admitted, is that reached by several authors. Cur- atello and Tarulli believe that the in- ternal secretion of the ovaries favors the oxidation of phosphorized organic substances, hydrocarbons, and fats. According to Gomes, it enhances oxi- dation and hydrolysis and favors the elimination of phosphates. ANIMAL EXTRACTS (SAJOUS). 771 Albert Robin and Maurice Binet have shown that there is during menstrua- tion an increase of the respiratory ex- changes. Keller, studying the general exchanges, found that there was in- creased nitrogen oxidation. We have ourselves found that menstruation, in itself, enhances vital functions and particularly the great function of gen- eral oxidation." Mathes noted a reduc- tion in the excretion of the phosphates, in women whose ovaries had been re- moved The ovary appears to preside in some way over the metabolism of inorganic matter, and, hence, aids in maintaining the composition of the blood. Thus when young bitches are castrated there is an initial reduction of the number of erythrocytes and amount of hemoglobin. Offergeld (Deut. med. Woch., June 22, 29, 1911). The investigations of the writers sustained Loewy and Richter so far as the reduction in metabolism after castration is concerned. Removal of the ovaries of dogs caused an in- crease in weight by lowering metab- olism in one from 12 to 17 per cent., and in the other from 6 to 14 per cent. Murlin and Bailey (Trans. Amer. Gynec. Soc; N. Y. Med. Jour., Aug. 11, 1917). PREPARATIONS AND DOSES. — The preparation in general use is the desiccated gland, available in the form of 2-grain tablets, which may be given in doses of 2 to 4 grains (0.132 to 0.26 Gm.) twice daily. The fresh organ may be employed in 10- to 15- grain (0.6 to 1.0 Gm.) doses where the phar- maceutical product is not available. As the patient becomes readily habituated to the remedy, it is best to begin with small doses and to increase them grad- ually. It owes its action to the cor- pus luteuni it contains. THERAPEUTICS.— As in the case of testicular preparations and spermin, ovarian extractives have been tried in a multitude of disorders with more or less benefit or without any whatever. Natural and Artificial Menopause. — In disorders occurring in the course of the physiological menopause, or when the latter is produced by bilateral oophorectomy, ovarian preparations have proven of considerable value in a large proportion of cases since Brown- Sequard first introduced their use. Ex- perience has shown, however, that the improvement lasts only as long as the agent is administered, and that, fur- thermore, certain phenomena: the palpitation, trembling, and "nervous- ness," disappear earlier than the oth- ers, i.e., the asthenia, flushes, irritabil- ity, and psychoses, though efifects in all symptoms, including the cutaneous disorders — especially acne rosacea and eczema — are promptly realized, some- times as early as the fourth day. These efifects are normally explained by the influence of the remedy on gen- eral oxidation and the improvement of the antitoxic functions of the blood, the imperfect hydrolysis of tissue wastes being the underlying cause of the phe- nomena other than the general asthenia. The best results are obtained in young w^omen who have grown obese after removal of the ovaries, or in whom obesity is due to ovarian in- sufficiency. In physiological meno- pause they are less marked, as a rule, and sometimes fail altogether to ap- pear. In such instances, good results may sometimes be obtained by giving simultaneously 1 grain (0.066 Gm.) desiccated thyroid, or by depending upon the latter remedy alone. In the amenorrhea of congenital ovarian in- sufficiency, desiccated ovary has caused the appearance of menstruation. W. E. Dixon, of Cambridge Univer- 778 ANIMAL EXTRACTS (SAJOUS). sity, recalls that the presence of ovarian tissue in the body, however small in amount, is sufficient to prevent the dis- tressing symptoms which frequently follow complete extirpation ; even trans- planted ovaries are sometimes able to prevent the menopause attending re- moval of the ovaries. Hence, the ben- eficial effects of ovarian preparations. Improvement has also been ob- tained by some observers in acne, prurigo, and eczema. They have been found to cause an increase of the red corpuscles in chlorosis and to afilord benefit in gout, epilepsy, exophthal- mic goiter and obesity, and also in dysmenorrhea. One must give an active prepara- tion in dosage sufficient for results, i.e., until the symptoms disappear. He had good results combating high blood-pressure at the climacteric, and arteriosclerosis may be thus pre- vented. All cases with hypofunction of the ovary are indications, espe- cially amenorrhea and so-called lacta- tion atrophy. In dysmenorrhea it is indicated if all other measures fail; likewise in hyperemesis, psychoses, especially dementia precox, postpuer- peral depression and hyperexcita- bility. C. B. Hucura (Jahrb. f. Psy- chiat. u. Neurol., xxxvi. 1916). In 2 cases of kraurosis vulvae, per- manent relief was obtained in 1 with ovarian extract; the other was tem- porarily improved after injecting the latter. The sole criterion was a change from the dry glistening un- yielding tissue to a soft, moist, and pinkish mucosa, which bore no evi- dence of scratching. G. Gellhorn (Trans. Amer. Gynec. Soc. ; N. Y. Med. Jour., Aug. 11, 1917). Of late, the general attention has been centered upon the therapeutic use of the essential structure of the ovary, the corpus luteum, although Graves and others have emphasized also the impor- tance of the interstitial cells. CORPUS LUTEUM ORGANO- THERAPY. The consensus of opinion up to now has been that the internal secretion of the ovary is produced by the corpus luteum. The function of the corpora lutea in the early stages of their life is to initiate growth processes in the uterine cavity by means of this internal secretion and subsequently to preside over the nidation and development of the ovum, and the cyclic engorgement preceding menstruation. The labors of Fraenkel confirming his previous inves- tigations have strongly sustained the internal secretion theory and its con- trolling influence over the above func- tions. The 2 most important prerequisites to success in the use of this drug are: 1. The selection of a preparation made exclusively from the corpora lutea of pregnant animals, and, 2, due attention to the fact that the action of the drug is frequently slow in as- serting itself, and that the drug should be given up only when thor- ough trial has demonstrated its lack of efticienc3\ L. T. de M. Sajous (X. Y. Med. Jour., Jan. 29, 1916). The relationship between character and degree of lutein structure to the disorders of menstruation, such as iTietrorrhagia and menorrhagia. was recently studied by the writer in 137 cases. The corpus luteum, he says, should be studied from the standpoint of origin in the lutein cells. Cases of amenorrhea show characteristically corpora lutea. It is absent in young girls and in the fetus, also in the menopause. With amenorrhea of lac- tation it is present, the functioning breast probably presenting an in- hibiting secretion. In metrorrhagia and menorrhagia there w-ere negative findings and no histological changes could be found connected with men- strual disturbances. The theca in- terna instead of advancing from lutein cells simply regresses. The ANIMAL EXTRACTS (SAJOUS). 779 granulosa cells are formed before the lutein cells, and the latter are formed from them. The internal secretion goes back into the blood. Hence the vascularization. E. Novak (Med. Rec, June 17. 1916). Summarizing the labors of Fraen- kel, Loeb, and Novak, the writer con- cludes that the corpus luteum makes possible the formation of maternal placenta by supplying a sensitizing substance to the uterine mucosa. Fix- ation of the embryo is aided by the activity of the corpora lutea. The corpus luteum is apparently essential for the development of the embryo earl}' in pregnancy. The presence of corpora lutea militates against ovula- tion, i.e., lengthens the sexual cj^cle, at least in the guinea-pig. The pres- ence or absence of corpora lutea means presence or absence of men- struation, and possibly their hj-po- or hyper- function means, in part at least, dysmenorrhea or menorrhagia. The activity of lutean secretion af- fects development of the mammary gland, even to free secretion of milk. E. T. Hermann (Minn. Med., May, 1918). As to the manner in which the sensi- tizing substance referred produces its effects, it is not explained. From my viewpoint they are the result of the presence in the corpus luteum of an energizing principle similar to the ad- renal active principle in organic com- bination with highly specialized specific nucleins. PREPARATIONS AND DOSES. — The preparations available include desiccated corpus luteum {glandulcr lutece desiccatcc), which may be given in 5- to 10- grain (0.3 to 0.6 Gm..) doses three times daily. It is usually administered before meals, but if, as is sometirnes the case, it causes gastric disturbances it may be admin- istered during, that is to say, in the course of, the meal. The term "lutein" is sometimes applied to the same prod- uct, but it is misleading, a.id its use should be discouraged. Considerable personal experience showed that corpus luteum should be given in sufficient doses, and over a long period of time to accomplish satisfactory results. It produces no toxic effect except a feeling of full- ness in the head or vertigo, and its action is not cumulative. H. E. Hap- pel (Med. Rec, May 19, 1917). A liquid preparation of corpus luteum extract is also available, 1 c.c. (16 minims) of which represents 20 milligrams {% grain) of the dried substance. THERAPEUTICS. — The indica- tions for desiccated luteum are similar to those for ovarian preparations. It is generally regarded as superior to them, however, particularly for the nervous phenomena of menopause, natural as well as operative, irregular or scanty menstruation particularly if accompanied by neurasthenia, dys- menorrhea, sexual anesthesia, pru- ritus vulvas and infantile uterus. The writer uses an extract derived from the ovaries of pregnant animals. He gives 5-grain doses (0.3 Gm.) 3 times every day. The blood-pressure of the patient should not be allowed to fall more than 15 mm. below the patient's normal pressure, and never below 90 mm. The particular condi- tions for which the drug is found serviceable are: Functional amenor- rhea or scanty menstruation; dys- menorrhea of ovarian origin; mani- festations of physiologic or artificial menopause, such as nervous or congestive disturbances of reflex origin (hot flushes, psychoneuroses, etc.), "neurasthenic" symptoms dur- ing menstrual life; sterility, not due to pyogenic infections or mechanical obstructions: where the function of 1 ovary is impaired, or 1 ovary has been removed, and the compensatory 780 ANIMAL EXTRACTS (SAJOUS). activity of the other is insufficient; repeated abortions, not due to disease or meclianical factors, and hyper- emesis in early pregnancy. W. T. Dannreuther (Jour. Amer. Med. As- soc, Jan. 31, 1914). Autotransplantation of the corpus luteum was resorted to by the writer in 2 cases. Both women complained of nausea and vomiting for several days after operation. In neither case was the implanted body palpable in the broad ligament at a later opera- tion. DeLee (Surg., Gynec. and Ob- stet., Jan., 1916). In menstrual epistaxis all styptic agents, even in local application, are contraindicated; the medication of choice should be physiological; that is to say, the secretions of the cor- pus luteum. The writer gives hypo- dermic injections of this substance and this treatment has generally been found sufficient for controlling even the most severe types of menstrual epistaxis. Bab (Miinch. med. Woch., Nov. l.\ 1917). Menopause symptoms of ovarian extirpation are largely ameliorated by ovarian extract. Its symptoms are vasomotor disturbances, hot flashes, head flushings, indigestion (perhaps due also to circulatory disturbance), the addition of weight mostly in the form of fat, sometimes nervous irri- tability, sleeplessness or the reverse, i.e., unusual daytime drowsiness and mental sluggishness. How many of these symptoms are due to loss of ovarian secretion, or to the sudden cessation of menstruation without pregnancy and consequently a stor- ing in the system without physio- logical need of the nutriments and salts of the blood which were pre- viously lost, has not been determined, but both are factors in the condition. The normal menopause or the cessa- tion of menstruation without preg- nancy at a younger age will cause more or less symptoms and ovarian feeding may markedly improve the condition. The writer considers the use of ovarian extracts in the following con- ditions: (1) after extirpation of the ovaries; (2) for menopause symp- toms, especially when the onset is abrupt; (3) for too slowly developing girls; (4) when there is an apparent subsecretion of the ovaries in older girls and women, especially when a long course of treatment is neces- sary; (5) in menstrual disturbances. He discusses the results obtained. He also records his results in the use of corpus luteum in: (1) amenor- rhea; (2) overweight; (3) dysmenor- rhea; (4) pregnancy; (5) menopause cases. It is unimportant whether it is the ovarian substance or the corpus luteum that furnishes the secretion that is most necessary for the mature woman's mental and physical health; it is a fact that many internal secre- ting glands are disturbed by the re- moval of the ovaries. Total removal of the ovarian tissue before puberty stops the development of the genital organs and of the breasts. Total re- moval after puberty stops menstrua- tion, causes artificial menopause, and multiplies the menopause symptoms and disturbances. The younger the adult woman so castrated, the more serious are the symptoms. Castrated women are often left in a serious mental and physical condition. Feed- ing these sufferers ovarian and corpus luteum extracts is only partially suc- cessful in ameliorating their condi- tion. The rules for operation for tubal and ovarian disease should be: 1. As much of the ovaries as are found healthy should be left. 2. If the op- eration of necessity destroys the cir- culation and therefore nutrition of the whole of both ovaries, large grafts from the healthy part of the ovaries should be placed in some loca- tion that will allow the ovarian tis- sue to readily obtain a blood supply and therefore live. If the ovarian transplant lives and functions, it should be remembered that it period- ically swells, and hence, in tense, non- dilatable tissue, maj- cause severe pain. The uterine wall, the peri- ANIMAL EXTRACTS (SAJOUS). 781 toneum, the labia majora. the mons veneris, the abdominal wall, and even the axilla have all been suggested as regions for implantation. If there is no healthy ovarian tis- sue for autografting, since total ex- tirpation of both diseased ovaries is not an emergency operation, the sur- geon connected with a large hospital generally could obtain a piece of health}- ovary from a non-syphilitic and non-tuberculous patient for trans- plantation into the woman to be cas- trated. The necessity for obtaining such ovarian tissue would be rare, as total extirpation is rarely needed. Of course the surgeon cannot decide that there is no healthy ovarian tissue until the time of the operation, but he should be prepared for such an emergenc}' when there is a probability of the necessity of total extirpation. Ovaries removed from healthy women after sudden accidental death, and properl}' preserved, would seem to be ideal tissue. If these engrafted ovaries or ovarian tissues live and function, it may be 2 or 3 months before the fact is known by any symptoms or signs in the patient. The signs of success are a general feeling of health, ab- sence or diminution of menopause symptoms, and menstruation. Such grafts may live for a time and then die, but more or less embryonic ovarian tissue may have had time to mature and to begin to furnish the secretion so much needed by the patient. Properly selected patients, who have had their ovaries removed for disease and who have ps3xhoses which are not cured by the adminis- tration of organic extracts, might well be treated by grafts of healthy human ovarian substance. O. T. Os- borne (N. Y. Med. Jour., cviii, 447, 1918). The writer used the liquid luteum extract hypodermically in 2 cases of repeated abortion without demon- strable cause with a successful result in both instances. The liquid extract was given intramuscularly in 1-c.c. (16 minim) doses, 36 being given the one case over a period of 2 months, and 32 in the second case over a period of 9 weeks. In one the 4 previous pregnancies had never gone beyond 314 months, while in the first case, the several abortions had re- curred about the third month. Such cases are referred to in text-books as "irritable uterus," but the writer ten- tatively attributes the repeated abor- tions to untimely absorption of the corpus luteum. J. Cooke Hirst (Amer. Jour, of Obstet., Apr., 1918). Through the use of corpus luteum there is a tendency in the body to retain nitrogen and put on flesh; it has a marked vasodilator effect; the development of the mammary gland depends upon the formation of cor- pus luteum; the fixation of the em- bryo, the formation of the decidua and menstruation depends upon the secretion of the corpus luteum. Ex- tracts of corpus luteum, however, do not replace the function of the nor- mal gland. It is a true pubert}- gland and an antagonist of the pituitary. Extract of corpus luteum causes dim- inution of nitrogen excretion in the urine, diminution of oxygen absorp- tion, unstable output of carbon diox- ide, increased activity of sweat glands, and a marked fall in blood-pressure. With these physiological data on hand, extract of corpus luteum has been used by clinicians in syndromes believed to be caused by disturbed sexual gland activity. The writer has tried it in the so-called "nervous sj'n- dromes'' associated with disturbed sexual gland function, and he care- fully watched the therapeutic results in a selected number of type cases. Satisfactory results were obtained and, in most instances, verj' rapidly in menstruation insanity? mild manic depressive insanity; menstruation psychosis; headaches occurring with menstrual disturbance; and symp- toms of diminution of hydrochloric acid with menstrual disturbance. There were no results in menstrual disturbance due to obstruction; in menopause due to surgery; cessation 782 ANIMAL EXTRACTS (SAJOUS). of menstruation with symptoms of acromegaly; in hysteria; or in or- ganic nervous disease. The clinical data following upon these observa tions were: 1, corpus luteum extract was effective only in the female; 2, it acted best when there was reason to believe the native corpus luteum was still present; 3, the administra- tion of the extract could not replace the function of the native corpus luteum in pregnancy and probably also not in menstruation; 4, when menstruation was discontinued by virtue of disturbance in the secretion of another gland, corpus luteum would not produce menstruation; 5, its action was more or less prompt and small doses were effective; and 6, corpus luteum extract, when effective, produced almost always the same chain of phenomena. H. Climenko (Trans. N. Y. Phys. Assoc; N. Y. Med. Jour., Feb. 15, 1919). Corpus luteum has been said to have caused a fall in blood-pressure, it does so in certain cases; in which absence of corpus luteum causes in- creased pressure. In abnormal cases, those deficient in corpus luteum. cor- pus luteum extract is helpful. In those cases in which corpus luteum is not the crucial factor, corpus luteum extract does nothing. It is an extension of the principle of nature that one can restore a disturbed cell to normal function more readily than one can put a normal cell into dis- function— the tendency of nature to self repair. Corpus luteum bears a similar relation to blood-pressure as does adrenalin. Whether one gets a rise or a fall of blood-pressure de- pends on the quantity given. Usu- ally the result is a fall. One very certain type of individual in whom corpus luteum has given more or less success as a therapeutic agent is a type of girl with certain masculine features; a slight tendency to a mustache, pubic hair growing to the umbilicus, etc. In those cases corpus luteum is almost invariably of service* In administering a glandular product, one is dealing with an en- zyme which acts by catalysis, not one which entered into combination with various metabolic processes, but helps metabolic processes along by its mere presence so that in adminis- tering it, it is sufficient to give it perhaps at times, only one day in seven, and not necessarily daily. Walter Timme (N. Y. Phys. Assoc; N. Y. Med. Jour., Feb. 15, 1919). The reason that the writer did not meet with much success was that he saw the patients 10 to 15 years after operation, and cases neglected to that extent do not respond to corpus luteum. Some do not respond when treatment is administered by the mouth. A. J. Rongy (X. Y. Phys. Assoc; X. Y. Med. Jour., Feb. 15, 1918). The writer found corpus luteum tremendously over-rated as regards its value. In some types of cases he gives cor- pus luteum to do the opposite of what others prescribe it for. If the patient complains that for so many days before menstruation she is nerv- ous, restless and irritable, it is an in- dex of what was happening under the stimulus of the ripening follicle of the ovaries. Associated with this is the stimulus to the thyroid and the activity of the pituitary. Dysmenor- rhea is much more due to the fact that the pituitary is involved than any action of the ovaries. There is an interglandular upset 13 times a j-ear. Many times there is no indication of this until after the birth of a second child, when glandular exhaustion makes a different individual. The writer terms this interglandular up- set "constitutional dysmenorrhea." Whether congenital or acquired it is one of the most important indices of the patient's condition. If every man in the medical profession were to pay attention to that factor, they would get a better idea of endocrines. X^ine-tenths of the prescriptions in the next 5 years would contain endocrine extracts. S. W. Bandler (N. Y. Phys. Assoc; N. Y. Med. Jour., Feb. 15, 1919). ANIMAL EXTRACTS (SAJOUS). 783 KIDNEY ORGANOTHERAPY. Brown-Sequard, having removed the kidneys and caused uremia, found that the injection of a glycerin extract of kidney prolonged the life of the animals as compared to those in which the same operation was not followed by the use of the kidney extract. This experiment, which has been repeated by others, forms the basis of the belief that the kidney produces an internal secretion. That such a conclusion may not be warranted is suggested by the fact that the kidneys, along with some of the organs so far reviewed, are also rich in adrenal tissue — the so-called "adre- nal rests" from hypernephroma some- times develops — and that as such they are capable, as an active factor in the immunizing functions of the body, of counteracting temporarily the toxemia or "uremia" brought on by removal of the kidneys. Indeed, the relief afiforded is but ephemeral, death being post- poned but one or two days in rabbits, in which Bitzou repeated Brown-Se- quard's experiments. Dromain and de Pradel Bra had also noticed that injec- tions of kidney extract lessened the fits of epilepsy, another toxemia. Dubois and Renaut have already, in fact, at- tributed antitoxic power to kidney ex tracts. That we are again dealing mainly with a manifestation of the adrenal principle is further suggested by its powerful blood-pressure-raising prop- erty. Tigerstedt and Bergman found that rennin possessed this power; Bin- gel and Strauss recently confirmed their observation, and found that its action corresponded with that of adrenal and pituitary extracts, those of other or- gans causing depressor eflfects. The use of pressure produced by kidney ex- tract was high, i.e., from 40 to 60 mm. Hg, and lasted from fifteen to thirty minutes. The authors concluded, more- over, that "the action of rennin, like that of adrenalin, is exerted in the mus- cles of the peripheral vessels." Its gen- eral action, however, is more like that of pituitary body extract, the adrenal principle being doubtless combined or- ganically, as in the pituitary, with bodies which prolong and perhaps con- trol advantageously the action of the former. Like adrenal preparations kid- ney extract also produces myosis. Even the oxidizing power I have at- tributed to the adrenal secretion seems to be reproduced ; Batty Sliaw, who also finds "very little justification for the existence of an internal secretion" in the kidney, remarks that "possibly nephrin and other renal preparations provide a means of stimulating oxida- tion in general, the kidney merely shar- ing in this oxidation" — a very accurate estimate from my viewpoint. Shaw adds, moreover, that "similar good re- sults have been reported as a result of treatment by means of spermin and testicular extract," both of which, as I have shown, also owe, in all probabil- ity, their therapeutic efifects to the adre- nal principle they contain. THERAPEUTICS AND DOSE. — The therapeutic application of kid- ney preparations has received consid- erable attention, and favorable results have been reported in about one-half of the cases of chronic nephritis, or Bright's disease, in which it was tried. The mode of action, in the light of the facts submitted above, is mainly an in- crease of the antitoxic power of the blood and diminution, therefore, of the irritation of renal apparatus. Page and Dardelin, for example, report marked amelioration in 18 cases, using a mac- eration prepared as follows: A very 784 ANIMAL EXTRACTS (SAJOUS). fresh kidney from a pig is cut into minute pieces, washed with fresh water to remove the excess of urine, then hashed and pounded into pulp. This pulp is put into 300 Gm. (9 ounces and 5 drams) of fresh water to which the physiological proportion of salt, 7.50 to 1000, has been added. It is then al- lowed to macerate for three hours, stirred occasionally, and kept in a cool place to avoid fermentation. The red water of the maceration is divided into three parts, to be drunk by the patient during the day. It is more conveniently given, however, in tablet form, as "nephritin," prepared in this country by Reed and Carnrick. Only the active substance of the kidney is used in this jMcparation, the dose being from 10 to 15 5-grain (0.33 Gm.) tablets daily in divided doses, given between meals. Kidney preparations have also been used with more or less advantage in puerperal intoxications and epilepsy, but their field is essentially the va- rious forms of nephritis, and particu- larly for the prevention of uremia. They also tend to increase diuresis and reduce the albumin. As stated above, however, favorable effects are to be ex- pected in about one-half of the cases. THYMUS ORGANOTHERAPY. In 1907, I submitted evidence which had led me to suggest that the function of the thymus was to supply an excess of phosphorus in organic combination during the growth of the body, i.e., particularly while the development of the osseous and nervous systems de- manded such a reserve. This was sus- tained by the recognized fact that certain diseases of children and ado- lescents, especially marasmus, rachitis, and trophic disorders of the brain and nervous system, were due. in part, to the functions of the thymus. The writer carried out the follow- ing experimental work. Young rab- bits belonging to the same litter were each trephined on the til>ia. Some of the animals were fed on thymus gland, the others serving as control animals. The ev^olution of the bone trauma in each was controlled by regularly repeated radiographic ex- aminations. The writer concludes that the exhibition of thymus gland hastens regeneration of bone trau- mata. At a given time in repair the difference consisted in the presence of a smaller bone defect, a normal osse- ous configuration and a moderate cal- lus, while the control animals offered an inverse condition. K. Glaesner (Berl. med. Woch., Nov. 25, 1918). While this is only adduced as a work- ing theory — the thymus having been the graveyard of many hypotheses — all that can be said for it is that it seems to account for the clinical results ob- tained under its use better than any hypothesis so far advanced, besides corresponding with the laboratory find- ings of its effects. In sexually immature rabbits, frag- ments of thymus autotransplanted into the subcutaneous tissue of the abdomen after thymectomy were found to take, grow and survive. This confirms other observers' re- sults that thymus removal hastens sexual maturity, and that utilization of rabbits for breeding hastens invo- lution of the thymus. The writers' experiments apply to the transplanted thymus as well. Marine and Manley (Jour. Labor, and Clin. Med., Oct., 1917). Whatever be the real function of the thymus, certain it is that its pro- duction of an internal secretion has not been proved. The evidence in favor of such a theory is but circum- stantial at best and very meager. It is equally difficult to prove that the thymus does not produce a secretion. Hoskins (Endocrinology, July-Sept., 1918). ANIMAL EXTRACTS (SAJOUS). 785 In the light of my own views the in the tissues, particularly in those of thymus supplies lymphocytes i.e., thy- the nervous system, which are ex- mocytes, exceedingly rich in nucleins tremely rich in phosphorus. Thymus, to the body at large for the purposes in- supplying phosphorus in organic com- dicated, but not an internal secretion. bination, replaces that lost by the nerv- THERAPEUTICS. — Diseases of ous system, thus procuring marked the Thyroid.— In simple goiter it was benefit in this one direction. As 5 first tried by Mikulicz, wdio obtained grains (0.33 Gm.) of the dried thymus sufficiently favorable results in 5 out of are equivalent to 30 grains (2 Gm.) of 11 cases to render operation unneces- the fresh gland, this dose can readily sary, at least for the time being. Rein- be given three times daily, bach considers it probably superior to Rachitis, or Rickets. — The same ex- thyroid because the unpleasant effects planation, i.e., the purveying of phos- of the latter are avoided ; for the same phorus in organic combination — to the reason it is especially suitable when osseous system, in the present connec- organotherapy has to be used contin- tion — accounts for the undoubted ben- uously. This view is based on the em- efit thymus has procured in this dis- ployment of thymus in a large number order. Mendel, having used thymus of cases in the Breslau clinic. Mikuhcz gland in 1^ to 3 drams (6 to 12 Gm.) gave from 2% to 4 drams (10 to 16 daily in over 100 cases, obtained marked Gm.) of the raw sheep thymus on benefit in a large proportion, but espe- bread three times a week, increasing cially in the nervous symptoms, includ- the dose slightly if required. ing spasm of the glottis. It had previ- In exophthalmic goiter it had proven ously been tried by Stoppato, but with- efficacious in the hands of Owen in out marked benefit. In Mendel's cases advanced cases, and also in those of both fresh and commercial tablets were Mande when other remedies had been tried, the cases being subdivided as fol- used fruitlessly. The latter gave 45 lows: 1, those which showed prodro- grains (3 Gm.) daily to a severe mal symptoms only; 2, those in which case, which greatly improved, relaps- deformity of the osseous system was ing whenever the treatment was inter- the chief feature ; 3, those marked by rupted. S. Solis-Cohen also advocates spasm of the glottis, and, 4, those in its use in this disease, having found which splenic enlargement was the most that it exerted its beneficial influence important sign. Marked improvement mainly upon the nervous symptoms of was noted in all after from three to the disease without affecting the ex- four weeks, and dentition and the clos- ophthalmus. Huston White found that ure of the fontanelle proceeded satis- the nervous symptoms were alone im- factorily. No untoward symptoms were proved. noted — a marked advantage over thy- These observations coincide with my roid preparations. In a case of stunted own view of the manner in which thy- growth, obviously of osseous origin, mus gland produces its beneficial ef- in a boy of 14 years, R. Webb Wilcox fects. The excess of thyroiodase pro- obtained 9^4 inches growth in three duced in exophthalmic goiter causes, years by the persistent use of 2 grains we have seen, too rapid oxidation of (0.13 Gm.) thymus night and morning. the phosphorus in organic combination The view that these effects are due 1-60 786 ANIMAL EXTRACTS (SAJOUS). to the addition of phosphorus in organic combination to the body is further sus- tained by the results of experimental observation by Hart and Nordmann, ' that the thymus had a definite relation to assimilation, and that it took an active part in the resistance of the or- ganism to infection. As my own inves- tigations have shown (see the second volume of "Internal Secretions," page 878), nucleoproteid, in so far as its phosphorus in organic combination is concerned, is an active participant in the immunizing process. Great relief, particularly from the pain of cancers, can be attained by the use of thymus extract, according to Takaki. This line of treatment was originally worked out by Gwyer, who showed that there was marked decrease, or even elimination, of pain. The glands used were received fresh. The fat was removed, and the glan- dular substance cut up and dried at a low temperature by a forced draught of air, then ground and sifted to a uniform powder. Of this a dose of from 1 to 4 drams was given three or four times a day. Ludlam has recommended thymus gland in de- mentia precox {q.v.)on the basis of six successful cases. BONE-MARROW ORGANO- THERAPY The bone-marrow being the source of red corpuscles, its preparations have been tried in pernicious anemia, the secondary anemias, chlorosis, ma- laria, leucocythemia, leukemia, Hodg- kin's disease, rickets, and other dis- orders of the osseous system. In all of these affections bone-marrow gave good results in some cases, while an equal number w^ere in no way influenced. This obviously suggests that its indica- tions coincide with certain phases or stages of the disease which have not as yet been determined. The average dose is 5 grains, after meals. BRAIN AND NERVE SUB- STANCE ORGANOTHERAPY. The belief, based on pure assumption, that brain and nerve substance possess or produce an internal secretion has never been sustained scientifically. The clinical results, though quite discordant, particularly in the neu- roses and psychoses in which these preparations have been tried, have shown a tendency to harmonize since the introduction by Sciallero of an oily extract. Page, who has obtained unusually good results in neurasthe- nia by means of injections of this ex- tract, ascribes them to its antitoxic and antispasmodic effects. W'asser- mann and Takaki had previously shown that tetanus toxin was neutralized by contact with brain substance, and that when a fatal dose of tetanus toxin was injected with brain substance the fatal effects were prevented. The same observations were made in the case of hydrophobia by Babes; in strychnine and morphine poisoning by W'idal and Nobecourt; in tetanus by Krokiewicz ; in epilepsy by Lion, and also Kaplan, using Poehl's opo- cerebrin — in accord with Dana's expe- rience several years earlier. Sciallero, who obtained encouraging results in neurasthenia, hysteria, chorea, tic, and epilepsy, used his oily extract "cephalopin" in doses varying from 1 to 5 c.c. (16 to 81 minims). No un- toward effects were obtained. Although it is very improbable that brain extracts injected into the tissues act as they do in the test-tube, it seems established that they act much as do the lecithins on the market, i.e., by furnish- ANIMAL EXTRACTS (SAJOUS). 787 ing phosphorus to the organism in an assimilable form, or as nucleoproteids in enhancing the immunizing process. Be this as it may, these substances seem to have produced effects which suggest that they should, not as yet, be set aside. The writer used brain extract in dementia, various forms of insanity, dementia precox, and melancholia, and other mental disorders with ma- terial improvement in some. It has the sedative effect of the synthetic hypnotics, without their danger. The extract used at first was prepared from the brains of fetal calves and was prepared by boiling finely-divided brain tissue in alcohol and ether, and preparing an emulsion from the de- posited material wath normal saline solution. This extract is rich in cholesterin and in a substance that reduces Fehling's solution. W. Maule Smith (Brit. Med. Jour.. Nov. 23, 1912). - The writer recalls the discovery of Howell that the so-called fibrin fer- ment is not really an enzyme, but a lipoid. As is well known, the fibrin ferment prepared from blood plate- lets has hemostatic properties and is at present extensively employed for this purpose. The author has pre- pared lipoid extracts by placing the brains of oxen in 3 equivalents of alcohol, shaking and decanting. The residue is gently strained through muslin and treated with threefold the amount of ether, shaken violently and filtered through cotton and paper. The dried filtrate is yellow, consists of Thudichum's kephalines and pos- sesses strong hemostatic properties, through its power of accelerating co- agulation. Hirschfelder (Berl. klin. Woch.. Sept. 13, 1915). A phosphatid extracted from brain tissue* variously known in the litera- ture and trade as thromboplastin or kephalin, was tried by the writer at the Johns Hopkins Hospital clinics, to hasten coagulation and hemostasis after surgical operations upon the genito-urinary apparatus and espe- cially prostatectomy. Packing was impregnated with kephalin and ap- plied to the raw surfaces. There was practically no bleeding. The writer uses kephalin gauze and also coats catheters with it. H. L. Cecil (Jour. Amer. Med. Assoc, Ixviii, 628, 1917). MAMMARY GLAND ORGANO- THERAPY. It is held by some that the mammary gland produces an internal secretion ; but the evidence is so scant that it can hardly be taken into account. Although mammary gland, introduced by Bell, of Glasgow, and in the United States by the late John H. Shober, has been used considerably, and has shown a marked stimulating action upon the uterus, the manner in which it produces this effect has remained obscure. An extract lowers somewhat, and but tem- porarily, the blood-pressure and the pulse. According to Shober, it dimin- ishes the blood supplied to the uterus and thus controls hemorrhage, its action resembling that of ergot, though free of the unpleasant effects of the latter drug. Mammary gland is prepared in the form of a tablet made of the desiccated gland of the sheep, each tablet repre- senting 20 grains (1.32 Gm.) of the fresh gland. The dose is from 3 to 6 tablets daily. The therapeutic application is re- stricted to the genital apparatus. In cases of uterine fibroids characterized by excessive menorrhagia and metror- rhagia the bleeding was found by Shober to be controlled in a few weeks and the periods become regular, nor- mal, and free from pain. There is im- provement in the patient's health and weight, and the tumors themselves di- minish in size up to a certain point. In 43 cases treated by Fedoroff. com- plete cure occurred in one-third, i.e.. 788 ANIMAL EXTRACTS (SAJOUS). 33 per cent. ; a reduction of volume in 43 per cent., and no result whatever in 14 per cent. The hemorrhages disap- peared completely in 80.3 per cent, of the cases. According to Fedoroff, the best effects are obtained when the mam- mary extract is used hypodermically. The patient is thus placed in a better condition for any needed operation, and often the necessity for an operation is postponed. Where there is evidence of inflammatory or degenerative changes, or when serious pressure symptoms are not controlled after a reasonable trial, operation should not be delayed. The mammary gland is also useful in cases of subinvolution unassociated with malignancy or structural changes. Mammary gland has also given good results, in the hands of Pozzi, in the uterine hemorrhages attending metritis of any kind. It decongests the organ and thus counteracts inflammation. It has also been recommended to as- sist uterine involution and to enhance lactation in agalactia. Here, again, the results reported have been antagonistic. The dose is 5 grains (0.32 Gm.), re- peated several times daily, preferably after meals. On the plea that the exciting cause of uterine fibroids and the accom- panying hemorrhages is uterine hy- peremia of ovarian origin, and that the antagonistic effect of the mam- mary principle is helpful because of its anti-ovarian influence, the writer found that in a large proportion of cases receiving mammary extract, the menorrhagia was effectively con- trolled and under its continued use large uterine fibroids often disappear even during the early reproductive period. The dose of mammary sub- stance was 10 grains (0.65 Gm.), 3 times a day; in severe cases 1 Gm. (15 grains), 4 times a day may be given with extract of ergot 0.2 Gm. (3 grains) and extract of hydrastis 0.1 Gm. (l)/2 grains) with each dose and also, in some cases, X-ray to the ovaries every 3 weeks. W. A. Briggs (Endocrinology, Apr., 1917). SPLEEN ORGANOTHERAPY. This is based mainly on the prevail- ing opinion that the spleen destroys red corpuscles and creates new ones, and that it produces some .sort of immuniz- ing body, its leucocytes, as in lymph- glands, being phagocytic. Extracts of spleen have been tried in various disorders, including ex- ophthalmic goiter, the secondary ane- mias, pernicious anemia, chlorosis, lymphadenoma, and leucocythemia, but the results have not been such as to warrant further trial. Rayle recom- mends it highly in tuberculosis. The writer administered fresh spleen substance with advantage in a number of cases of anemia. It reduced the proportion of nucleated reds in a remarkable manner and the clinical experiences were paralleled by similar findings in experiments upon animals. Brinchmann (Norsk Mag. f. Laegevidenskaben, Nov., 1916). Pancot, Carpenter, and others claim to have obtained good results from splenic extract in the treatment of malaria. Lemansky found that it en- hanced the action of quinine. HEPATIC ORGANOTHERAPY. Besides the functions carried on by the bile, which will be referred to be- low, the liver subserves several useful roles. It is endowed with important antitoxic functions, all foodstuffs ab- sorbed through the intestinal mucosa entering the organ through the portal system for this purpose. It supplies, out of the glycogen it forms, the blood and tissues the sugar they contain ; it takes part in the metabolism of nitrog- enous substances and forms urea. That ANIMAL EXTRACTS (SAJOUS). 789 these many phases of usefulness should have suggested the use of hepatic sub- stance is not surprising. Gilbert and Carnot found it useful in various con- ditions. In diabetes liver extract was found to act with considerable energy ; in some cases, however, the sugar was promptly diminished, even to nil occasionally, while in others it increased it. I have called attention to the fact that two forms of diabetes, the sthenic and as- thenic, should be clearly distinguished from each other, the treatment of one form being pernicious in the other. It is in the asthenic form that hepatic ex- tract will be found of value. Lere- boullet has also observed beneficial effects in some cases. One important feature of liver ther- apy is that, as emphasized by practical experience, the remedy causes diuresis in subjects who suffer from hepatic in- sufficiency in some form and par- ticularly when it occurs in the course of cirrhosis. The diuresis is also ac- companied by increased urea elimina- tion. In alcoholic cirrhosis it was also found of value by Gilbert and Carnot. The edema, jaundice, and hemorrhages were kept in abeyance in a case re- ported, returning whenever the use of liver extract was interrupted. The coagulating action of liver on the blood, shown by Gilbert and Car- not, was carefully studied by Berthe. The patients on whom the observations were made were tuberculous, and had suffered repeatedly from hemoptysis, which had not responded to any ordi- nary treatment. In all cases the results were rapid. The method was also tried in cases of epistaxis and metrorrhagia. The method consisted in giving an ex- tract of liver, about 3 drams (12 Gm.) for a dose, in tepid soup. This amount will in many cases sufifice, but can be repeated when necessary. It can also be administered per rectum in the same dose. One of the best and most suitable preparations *is the desic- cated liver. The glycerin extract is also efficacious. Should it not be pos- sible to procure a ready-made extract, an emulsion of liver freshly prepared, and given in the form of an enema, seems to act perfectly well, 3 to 6 ounces (94 to 186 Gm.) being finely chopped up and then rubbed up with water, about AY> ounces (140 Gm.) of liver being used. Fresh pigs' liver is one of the best sources of preparation. Liver extract, now available on the market, has also been used with advan- tage in chronic gastrointestinal intox- ication, the object being to check the' growth of bacterial flora. Biliary acids, referred to below, are, however, prefer- able. A convenient way is to use the biliary extract in suppositories. BILE, BILE-SALTS, AND BIL- IARY EXTRACTS. The use of hile in therapeutics is based on a sounder basis than that of several of the foregoing agents, its ex- citomotor action on the intestine, now fully demonstrated, serving various use- ful purposes. It counteracts constipa- tion due to intestinal atony, and thus prevents autointoxication of intestinal origin, which, in turn, produces cholan- gitis by allowing the return into the portal system of excretory products which should have escaped normally with the intestinal discharges. Again, bile, as shown by Pawlow, is a physio- logical auxiliary to the pancreatic juice, augmenting its activity threefold. As is well known also, bile, or gall, in- creases the solubility of cholesterin, thus preventing the formation of gall- 790 ANIMAL EXTRACTS (SAJOUS). stones. Bile is also endowed with anti- toxic properties. The therapeutic use of bile or bile constituents is thus based on a solid foundation. They may be used as stated abov^,in constipation and putre- faction due to hepatic and intestinal atony, autointoxication of intestinal origin, in cholangitis and the resulting jaundice, and also to prevent the for- mation of gall-stones. They have also been used advantageously in enteroco- litis in its membranous form. Mucomembranous enterocolitis and constipation being the result of insuffi- ciency of the bihary secretion, their treatment becomes simple. The general indications are: (1) reduction to a minimum of the quantity of toxic and putrefactive products in the intestine by an appropriate diet ; (2) shortening of the period of transit of food through the alimentary canal and prevention of the coagulation of mucus by the use of a cholagogue, the best of which is bile itself. The writer uses an extract de- void of putrescible nucleoalbumins. which he has termed antimucose, avail- able in 0.20-Gm. (3.1 grains) dragees ; suppositories, and ampules of 50 c.c. (1.7 fluidounces) in which the biliary substances, dissolved in water, occur in the concentration of normal bile. H. Nepper (Monthly Cyclopedia and Med. Bull., Jan., 1912). The writer found bile a powerfully cytolytic agent, owing to the coen- zyme or activating action of its con- stituents on the autolytic enzymes or processes. Whole bile was found more powerful though less penetrat- ing than corresponding concentra- tions of either of the bile salts. Tatum (Jour, of Biol. Chemistry, Oct., 1916). Although cholic acid is the most active of the bile-salts, salts of glyco- cholic or taurocholic acid are preferred. They possess all the therapeutic prop- erties of oxgall. The sodium glyco- cholate or taurocholate can be con- veniently used in }4- to 3- grain (0.032 to 0.19 Gm.) doses three times a day. Or, the extract of bile may be given in 5- to 15- grain (0.32 to 1.0 Gm.) doses after meals, with a draught of water. Bile may also be injected into the rectum to cause its evacuation. This is especially valu- able in paralytic ileus, postoperative and peritonitic atony, or paresis of the intestine from any cause. C. E. DE M. Sajous Philadelphia. r \ RC Sa ,10113, Charles Euchariste de a Medici s S3 5 Analytic cyclopedia of v.l practical medicine 9th rev. ed. Biological & Medical PLEASE DO NOT REMOVE CARDS OR SLIPS FROM THIS POCKET UNIVERSITY OF TORONTO LIBRARY >■